Cellular adhesion and the extracellular matrix - Week 24 Flashcards
1
Q
what are Fibroblasts, what is there structure, what is there function, how are they stimulated, what happens if they are over excreted
A
Fibroblasts are connective tissue cells that synthesize and secrete the extracellular matrix (ECM).
They are spindle-shaped, motile, and play a crucial role in wound healing by producing ECM components.
Inflammatory cells stimulate fibroblasts through TGF-β.
Excessive secretion of ECM components by fibroblasts can lead to fibrosis, disrupting tissue structure and function.
2
Q
what are white adipocytes, and what do they regulate
A
White adipocytes, known as adipocytes, are specialized cells that store fat and secrete a hormone called leptin, which regulates appetite and energy expenditure.
3
Q
What distinguishes brown/beige adipocytes from white adipocytes in terms of mitochondria, cytochromes, iron, coloration, and their roles in energy processing and thermogenesis?
A
brown and beige adipocytes are involved in energy processing and thermogenesis (which is the production of heat). These cells contain a higher number of mitochondria compared to white adipocytes, and their mitochondria are enriched with cytochromes and iron, giving them their characteristic brown color.
4
Q
How does brown fat abundance differ between newborn babies/hibernating animals and adult humans/non-hibernating animals
A
Both newborn babies and hibernating animals have higher amounts of brown fat compared to adult humans and non-hibernating animals
5
Q
where do blood cells originate from
A
Blood cells, including red blood cells (erythrocytes), white blood cells (leukocytes), and platelets (thrombocytes), originate from pluripotent stem cells in the bone marrow.
6
Q
what is the function of platelets
A
Platelets, also known as thrombocytes, play a crucial role in blood clotting and the repair of minor defects in blood vessels.
7
Q
do platelets have a nucleus
A
Platelets are anucleate, which means they do not have a nucleus, but they contain other cellular components, including granules.
8
Q
what are the 2 types of granules in platelets and what do they contain
A
There are two main types of granules in platelets: dense granules and alpha granules.
Dense granules contain substances such as adenosine diphosphate (ADP) and serotonin.
Alpha granules contain various proteins, including glycoproteins and platelet-derived growth factor (PDGF).
9
Q
what are TLRs are what is there function
A
Toll-like receptors (TLRs) are a type of pattern recognition receptor (PRR) that play a critical role in the innate immune response by recognizing and responding to structurally conserved molecules derived from microbes.
10
Q
where are TLRs expressed
A
TLRs are single-pass membrane-spanning receptors expressed on sentinel cells, such as macrophages and dendritic cells.
11
Q
what are the 2 different routes that can activate TLRs
A
TLRs can be activated by two different routes: signal from the plasma membrane (PM) and signal from endosomes.
12
Q
what is blood cell differentiation and how is it regulated
A
Blood cell differentiation is a complex process that involves the specialization of hematopoietic stem cells into distinct types of blood cells, such as red blood cells (erythrocytes), white blood cells (leukocytes), and platelets (thrombocytes).
This process is regulated by gene expression, which is controlled by transcription factors.
13
Q
what is the extracellular matrix and what is its function
A
The extracellular matrix (ECM) is a complex network of proteins and carbohydrates that fills the spaces between cells in animal tissues. It provides structural support, helps maintain tissue integrity, and regulates cellular behavior, analogous to cell walls in, fungi, algae, and higher plants, which also provide structural support to cells.
14
Q
how are animal cells intrinsically linked to other cells and the ECM
A
Many animal cells are intrinsically linked to other cells and to the ECM through cell surface molecules that bind to other cells or components of the ECM.
Cell surface molecules, such as integrins and other cell adhesion molecules, play a crucial role in cell-ECM and cell-cell interactions.
15
Q
How does the extracellular matrix (ECM) contribute to the composition and cellular environment in tissues such as bone, cartilage, and connective tissues
A
In tissues like bone, cartilage, and connective tissues, the ECM makes up a significant portion of the tissue composition or provides a gelatinous matrix for cells.
16
Q
where are fibroblasts found and what do they produce
A
Fibroblasts are common cells in connective tissues that produce and maintain the ECM.
17
Q
in animals, where are cells embedded
A
In animals, cells are embedded within the ECM, which consists of proteins, such as collagen and fibronectin, and polysaccharides.
18
Q
what is the function of the ECM
A
Extracellular matrix: ECM Function
* Provides structural support to cells and tissues
* Important role in regulating cell behavior
* Facilitates Cell to cell interaction and thus
communication
19
Q
which is the structure of fibrous, and what are 2 examples of fibrous proteins
A
Fibrous proteins are a type of protein that have a unique structural arrangement, characterized by long, slender fibers or threads. Two examples of fibrous proteins are collagen and elastin.
20
Q
what is the function of adhesion proteins
A
Adhesion proteins are a group of proteins that play a crucial role in linking components of the extracellular matrix (ECM) to each other and to cells, thereby providing structural support and stability to tissues.
21
Q
name 6 types of adhension proteins
A
- Fibronectin
- Fibrilin
- Laminin
- Tenascin
- Vitronectin
- Osteonectin
22
Q
what are polysaccharides, what are they composed of and what is their function
A
Polysaccharides are complex carbohydrates composed of long chains of sugar molecules. In the extracellular matrix (ECM), polysaccharides play important roles in creating a gel-like environment that provides structural support and facilitates cell signaling.
23
Q
what are the 2 types of polysaccharides found in the ECM
A
Glycosaminoglycans (GAGs) and proteoglycans are two types of polysaccharides found in the extracellular matrix (ECM).
24
Q
what are all the different types of GAGs and proteoglycans
A
all types of glycosaminoglycans (GAGs) and proteoglycans (which are components of the extracellular matrix in various tissues in the body) are:
- Biglycan
- Agrecan
- Versican
- Neurocan
- Heparan sulphate
- Kondroitin 4-sulphate
- Kondroitin 6-sulphate
- Deparan sulphate
- Hyaluronan
25
what amount and type of extracellular matrix component in there in different matrices, with examples
Different matrices have different amounts and types of extracellular matrix components depending on the tissue type and function.
For example, tendons are composed mainly of fibrous proteins such as collagen. Cartilage, on the other hand, is rich in proteoglycans, and bone is primarily composed of collagen fibers and calcium phosphate crystals.
26
what is the basal lamina and what is its function
The basal lamina is a thin layer of extracellular matrix that underlies and supports epithelial cells, providing a physical barrier between the epithelium and underlying tissues.
27
what does the basal lamina surround and why
In addition to its role in epithelial tissue, the basal lamina also surrounds muscle cells, adipose cells, and peripheral nerves, in order to help to anchor these cells in place and provide structural support.
28
where is the basal lamina present the most
While the basal lamina is present in many tissues throughout the body, it is most abundant in connective tissues.
29
what are the different types of connective tissues
different types of connective tissues are:
>loose connective tissue
>Bone
>tendon
>cartilage
30
what is the most abundant fibrous protein in the human body as what is its function
Collagen is the most abundant fibrous protein in the human body and its function is to provide structural support to many tissues.
31
What is the role of collagen in the human body, and how does its triple helical structure contribute to its function? Additionally, what are the typical amino acids found in the X and Y positions of the Gly-X-Y repeating pattern, and how do they contribute to the stability of the triple helix
Collagen is the most abundant fibrous protein in the human body and provides structural support to many tissues such as skin, bone, cartilage, and tendons. Collagen forms triple helices, which are composed of three protein chains called alpha chains, that are tightly coiled around each other. The triple helix domains consist of repeats of the amino acid sequence Gly-X-Y, where every third position is occupied by glycine, which is the smallest amino acid. X is typically proline, which packs the helices closely, and Y is usually hydroxyproline, which is synthesized in the endoplasmic reticulum (ER) and helps stabilize the helix by forming hydrogen bonds.
32
What are some of the tissues in the human body where type I collagen can be found, and what is the structure of the polypeptide chains in type I collagen
Type I collagen is the most abundant collagen in the human body, and it is found in tissues such as bone, skin, tendons, and ligaments. The polypeptide chains in type I collagen have about 330 Gly-X-Y repeats, which form triple helical molecules that are secreted from cells through the endoplasmic reticulum (ER) and Golgi apparatus.
33
How do collagen molecules form strong fibrils and fibers, and what is the role of cross-links in their structure
when collegen is once secreted, the triple helical molecules associate with each other in a staggered array to form collagen fibrils. Covalent cross-links between lysine and hydroxylysine side chains strengthen the fibrils, making them resistant to mechanical stress. The fibrils further associate to form collagen fibers that can be several micrometers in diameter.
34
what is the function of collagen fibers
Collagen fibers provide structural support and mechanical strength to tissues, and they also play a role in cell signaling and tissue repair.
35
What are the different cell types that can secrete collagen fibers and which cell type is the principal producer of collagen fibers in the extracellular matrix (ECM) of connective tissue
Fibroblasts are the principal producers of collagen fibers, which are the most numerous component of the extracellular matrix (ECM) in connective tissue. In addition to fibroblasts, other cell types such as epithelial and smooth muscle cells can also secrete their own type-IV collagen.
36
what is the structure of collagen fibers and how does their structure help their function
Collagen fibers have a wavy, non-uniform appearance and are bundled together in a way that allows them to branch and anastomose, forming a complex network. Although the fibers themselves do not branch, their branching and anastomosing allows for increased strength and support of the tissue.
37
how does collagen fibers look under a microscope
Under the electron microscope, individual collagen fibers are composed of smaller, repeating units called fibrils, which exhibit a periodicity of cross striations every 67 nm along their length. This gives collagen fibers their characteristic banding pattern.
38
what are different types of collagen found through the body, and where are they found
Collagen is a diverse family of proteins that are found in various tissues throughout the body. Here are some common types of collagen:
- Fibrillar collagens: These are the most abundant type of collagen and form the characteristic fibrils seen in connective tissue.
- Fibril-associated collagens: These collagens do not form fibrils on their own but instead bind to fibrils and help to stabilize and organize the ECM.
- Network-forming collagens: These collagens have interruptions in their helical structure, which allows them to form a mesh-like network in the ECM.
- Anchoring fibrils: These collagens are found in the basement membrane and help to anchor it to the underlying connective tissue.
- Transmembrane collagens: These are collagen proteins that are embedded in the cell membrane and participate in cell-matrix interactions.
39
what is the extracellular matrix (ECM) composed of
The extracellular matrix (ECM) is composed of a complex mixture of proteins, proteoglycans, and glycosaminoglycans (GAGs).
40
what is the structure of GAGs and what are they composed of
GAGs are long, unbranched polysaccharides that are composed of repeating disaccharide units. One of the sugar residues is usually N-acetylglucosamine (GlcNAc) or N-acetylgalactosamine (GalNAc), and the other sugar residue is typically a negatively charged acid sugar, such as glucuronic acid or iduronic acid.
41
how are the repeating disaccharides units of GAGs connected
The repeating disaccharide units of GAGs are connected by a specific type of covalent bond known as a glycosidic linkage.
42
How do sulfate groups in GAGs contribute to hydrated gel formation in the ECM and why is this important for tissue hydration and mechanical properties
The negatively charged sulfate groups present in GAGs contribute to their ability to bind to positively charged ions (such as sodium and calcium) creating a high osmotic pressure and attracting water molecules. This results in the formation of hydrated gels within the extracellular matrix (ECM), which helps to maintain tissue hydration and mechanical properties.
43
how are proteoglycans formed and what is their function dependent on
GAGs are often covalently linked to proteins, forming proteoglycans, which have a wide range of functions depending on the specific type and location within the ECM.
44
where is fibronectin found
Fibronectin is one of the main proteins found in the ECM of connective tissues, such as skin, bone, and blood vessels.
45
what does fibronectin bind to and why
Fibronectin is a large homodimeric protein that can bind to other ECM components, such as collagen and glycosaminoglycans (GAGs), as well as to cell surface receptors. This binding promotes the attachment of cells to the ECM, which is important for tissue development and maintenance.
46
where is laminin found, what is it composed of and what structure does it assemble
Laminin is another important adhesion protein found in the extracellular matrix. It is a heterotrimeric protein composed of α, β, and γ chains that assemble into a cross-linked network.
47
what molecules does laminin bind to and why
Laminin has binding sites for a variety of molecules, including cell surface receptors like integrins, as well as type IV collagen and proteoglycans. This is because this allows laminin to link cells to the extracellular matrix and promote cell adhesion and migration.
48
what is important for the formation of basal lamina, what is the basal lamina and what is the function of basal lamina
Laminin is particularly important in the formation of the basal lamina, which is a specialized ECM layer that separates epithelial cells from underlying connective tissues. The basal lamina provides structural support for tissues and helps to regulate cell behavior.
49
what are the 3 types of adhesions and junctions
There are three main types of cell adhesions and junctions:
- Cell-cell adhesions
- Cell- ECM adhesions
- ECM-ECM
50
what are Ig-CAMs, what is their function and where are they expressed
Ig-CAMs, or immunoglobulin-cell adhesion molecules, are a family of proteins that play important roles in cell recognition, binding, and adhesion. They are expressed in a variety of cell types, including immune cells, endothelial cells, and neurons in the brain.
51
which domain of Ig-CAMs can interact with signalling molecule and what does this allow
The intracellular domains of Ig-CAMs can also interact with signaling molecules, allowing for downstream signaling events that can impact cell behavior.
52
what is the function of cell-cell interactions
Cell-cell interactions play a critical role in the development and function of multicellular organisms.
53
what are the 2 types of cell-cell interactions and why are they important
Transient interactions, such as the activation of immune cells and migration to injury sites, are important for responding to environmental stimuli. Stable interactions, on the other hand, are important for the organization of tissues and maintaining the structural integrity of organs.
54
what are cell-cell junctions
Cell-cell junctions are specialized structures that allow rapid communication between adjacent cells.
55
during embryo development, what do cells adhere to and why
During embryo development, cells from one tissue will typically adhere to cells of the same tissue rather than cells of a different tissue. This process is essential for the proper organization and differentiation of tissues and organs.
56
what are the 4 major groups of CAMs involved in cell-cell adhesion
There are four major groups of CAMs involved in cell-cell adhesion:
- selectins,
- integrins,
- immunoglobulin (Ig) superfamily,
- cadherins.
57
what are cell adhesion processes dependent on
Many cell adhesion processes are divalent cation-dependent, meaning they require the presence of Ca2+, Mg2+, or Mn2+ ions for proper function.
58
what are selectins and what is there function
Selectins are a family of transmembrane glycoproteins that are involved in transient interactions between leukocytes and endothelial cells. These interactions play a critical role in the process of leukocyte extravasation, which is the migration of leukocytes from the bloodstream to sites of tissue inflammation.
59
during the initial phase of leukocyte extravasation, what do selectins interact with and what does the interaction cause
During the initial phase of leukocyte extravasation, selectins on the surface of endothelial cells interact with their ligands on the surface of leukocytes. This interaction causes the leukocytes to slow down and roll along the endothelial surface.
60
how is the formation of stable adhension between leukocytes and endothelial made and what does the interaction between leukocytes and endothelial result in
The next phase afterintial phase of leukocyte extravasation involves the formation of stable adhesions between the leukocytes and endothelial cells. This is mediated by the binding of integrins on the surface of leukocytes to intercellular adhesion molecules (ICAMs) on the surface of endothelial cells. This interaction results in the flattening of leukocytes against the endothelial surface and the initiation of signaling pathways that promote their migration across the endothelial barrier.
61
what are the 4 types of cell-cell connections in animal cells
The four types of Cell-Cell connections in animal cells are:
- Adherens Junctions
- Desmosomes
- Tight Junctions
- Gap Junctions
62
what are adherens junctions and what are they composed of
Adherens junctions are a type of intercellular junctions that are important for cell-cell adhesion and tissue integrity. They are composed of cadherin proteins that mediate calcium-dependent adhesion between adjacent cells.
63
what are cadherin proteins and what do they interact with
Cadherin proteins are transmembrane proteins that extend through the plasma membrane and interact with cadherins on adjacent cells to form homophilic bonds.
64
what is known as the caherin-catenin complex
The intracellular domain of cadherin interacts with a complex of proteins including β-catenin, p120, and α-catenin, which are collectively known as the cadherin-catenin complex.
65
How do β-catenin and p120 contribute to the stability of adherens junctions, and what is the role of α-catenin in this process
β-catenin and p120 bind to the cytoplasmic domain of cadherin and help maintain its stability. β-catenin also interacts with α-catenin, which in turn binds to actin filaments of the cytoskeleton. This linkage between cadherin and actin filaments provides mechanical stability to the adherens junctions.
66
what is the function of desmosomes, what do they link and what are they composed of
Desmosomes are intercellular junctions that provide mechanical strength and resistance to shearing forces in tissues subjected to mechanical stress.
They link the intermediate filaments of adjacent cells and are composed of transmembrane cadherins, desmoglein, and desmocollin, which bind by heterophilic interactions across the junction.
67
what does the cytoplasmic domain of desmoglein and desmocollin interacts with and what do they in turn bind to
The cytoplasmic domain of desmoglein and desmocollin interacts with plakoglobin and plakophilin, which in turn bind to the intermediate filament binding protein, desmoplakin.
68
what does the linkage between the transmembrane cadherins and the intermediate filaments provide
The linkage between the transmembrane cadherins and the intermediate filaments provides mechanical stability to the desmosomes
69
how is the network of intercellular connections that maintains tissue structure and function made
Tight junctions primarily seal the spaces between cells to maintain tissue integrity and prevent the passage of substances. Adherens junctions and desmosomes provide strong adhesive connections between cells. Together, they form a network of intercellular connections that maintain tissue structure and function.
70
what do tight junction in epithelial cells create
Tight junctions in epithelial cells create a physical barrier that seals the space between adjacent cells, preventing the free movement of molecules and ions between them.
71
what does the separation of the apical and basolateral domain ensure
The separation of the apical and basolateral domains of the plasma membrane ensures that the functions of these two domains remain distinct and prevents the free diffusion of lipids and membrane proteins between them.
72
what are different types of transmembrane proteins and what are they anchored to
transmembrane proteins such as occludin, claudin, and junctional adhesion molecule (JAM) are anchored on F-actin in the cytoskeleton of epithelial cells
73
what do the transmembrane proteins interact with and why is a tight seal formed
transmembrane proteins interact with similar proteins on the adjacent cell, forming a tight seal that prevents the free diffusion of molecules and ions between cells.
74
what are gap junctions, what do they do, what are they composed of and what can't pass through gap junctions
Gap junctions are specialized structures in the plasma membrane that form open channels between adjacent cells, allowing for the direct transfer of ions and small molecules.
Gap junctions are composed of protein subunits called connexins, which form a channel or pore between cells.
Proteins and nucleic acids are too large to pass through gap junctions.
75
in the heart what does passage of ions through gap junctions between neighboring cells allow
In tissues such as the heart, the passage of ions through gap junctions between neighboring cells allows for rapid and coordinated responses of cells.
76
why can molecules such as cAMP and Ca2+ are able to pass through the gap junctions
some signaling molecules such as cyclic AMP (cAMP) and calcium ions (Ca2+) can also pass through gap junctions to allow for the coordinated regulation of cellular responses in tissues.
77
what are gap junctions, what are they composed of
Gap junctions are specialized intercellular channels that allow direct communication between adjacent cells. These channels are composed of transmembrane proteins called connexins, which oligomerize to form hexameric structures known as connexons.
78
why does each connexon have a central aqueous pore
Each connexon has a central aqueous pore that allows small molecules and ions to pass through.
79
how are open channels formed and what do they enable
When connexons in the plasma membrane of adjacent cells align, they form open channels that connect the cytoplasm of the two cells, enabling the exchange of molecules and ions between them.
80
in nerve cells, what do gap junctions form
gap junctions can form an electrical synapse, which allows for the rapid transmission of electrical signals between cells.
81
how is the opening and closing of connexons regulated
The opening and closing of connexons can be regulated by various factors such as voltage, pH, and signaling molecules.
82
what are integrins, what is there function and what are they composed of
Integrins are a family of transmembrane receptors that play a crucial role in cell adhesion and signaling. They are composed of two subunits, alpha (α) and beta (β), which together form a heterodimeric complex.
83
what does integrins bind to, with examples
Integrins bind to various extracellular matrix molecules, such as collagen, fibronectin, and laminin, as well as to cell adhesion molecules, including immunoglobulin superfamily members.
84
what functions is integrins involved in, and what do they anchor to
Integrins are also involved in cell migration, proliferation, differentiation, and survival, and they anchor the cytoskeleton to the extracellular matrix.
85
what are the 2 types of cell-matrix junction and where do they play a role
Focal adhesions and focal complexes are two types of cell-matrix junctions that play important roles in cell adhesion and migration.
86
what are focal adhesions composed of
Focal adhesions are large, well-defined structures that are composed of integrins, actin filaments, and various cytoplasmic proteins such as talin and vinculin.
87
what is the function of focal adhesions
focal adhensions are structures that form a mechanical link between the cell and the extracellular matrix, and there function is in transmitting mechanical signals from the extracellular environment to the cell's internal signaling pathways.
88
Which proteins are involved in anchoring actin filaments to the extracellular matrix during the assembly of focal adhesions
The assembly of focal adhesions involves the recruitment of talin, vinculin, and α-actinin to the β subunits of integrins, which then anchor the actin filaments to the extracellular matrix.
89
what are focal complexes composed of
Focal complexes are smaller and less well-defined structures in comparison to focal adhesions. they are composed of a small group of integrins and cytoplasmic proteins such as talin, vinculin, α-actinin, and formin.
90
what is the function of focal complexes
focal complexes are structures that are involved in the early stages of cell adhesion and are thought to play a role in the initial clustering of integrins at the cell-matrix interface.
91
how is formin recruited and what is their function
Formin, which is recruited to focal complexes, initiates the formation of actin filaments, which then bundle together to form larger structures.
92
what are integrins, what do they bind to and what allows the formation of cell-cell and cell-matrix adhesions
Integrins are transmembrane receptors that can bind to various extracellular matrix components such as collagen, fibronectin, and laminin.
Integrins can also bind to other proteins on the cell surface, such as other integrins or cadherins, which allows for the formation of various cell-cell and cell-matrix adhesions.
93
what is one important features of integrins
One important feature of integrins is their ability to reversibly switch between active and inactive states.
94
how are integrins when they are inactive and how do integrins change their conformation in response to external signals and what effect does this have on their affinity for extracellular matrix components
In their inactive state, the integrin heads are turned close to the cell surface, and the receptor has a low affinity for extracellular matrix components. However, upon receiving external signals from the extracellular environment, integrins can undergo conformational changes that extend their heads towards the matrix, which increases their affinity for matrix components.
95
what is important for the formation of focal adhesions
The conformational change of integrins is important for the formation of focal adhesions, which are specialized structures that form at the leading edge of migrating cells.
96
What is the mechanism behind the disassembly of focal adhesions at the trailing edge of migrating cells, and how does this process contribute to the cell's ability to move forward
Focal adhesions allow the cell to attach to the extracellular matrix and generate the necessary forces to move forward. As the cell moves forward, the focal adhesions disassemble at the trailing edge, allowing the cell to detach and move forward again.
97
what are hemidesmosomes, what is there function and what are they composed of
Hemidesmosomes are specialized cell-matrix adhesion structures that anchor epithelial cells to the underlying basal lamina.
Hemidesmosomes are composed of integrins, which are transmembrane receptors that bind to extracellular matrix components, and cytoplasmic plaque proteins.
98
What is the role of the β4 subunit in hemidesmosomes, and how does it interact with cytoplasmic plaque proteins to anchor intermediate filaments to the basal lamina
In hemidesmosomes, the α6β4 integrin heterodimer is the primary transmembrane receptor that binds to laminins, a major component of the basal lamina. The β4 subunit has a long cytoplasmic tail that interacts with several cytoplasmic plaque proteins, including plectin and BP230/BP180. These cytoplasmic plaque proteins, in turn, bind to intermediate filaments, which are composed of keratin proteins in epithelial cells.
99
what are the 2 main types of tissue in our body
Epithelial tissues and mesenchymal tissues are two of the main types of tissues in the body.
100
who is Elizabeth Dexter Betty Hay, where do she make contributions and what was she an advocate for
Elizabeth Dexter "Betty" Hay was an embryologist who made important contributions to our understanding of mesenchyme and its role in embryonic development.
Hay was also a strong advocate for women in science.
101
what are benign tumours, where can they occur and how do they arise
Benign tumors are non-cancerous growths that arise from cells in the body but do not spread to other parts of the body. They can occur in almost any tissue or organ, and they arise with great frequency in the population. However, benign tumors usually grow slowly and are well-defined, which means they tend to remain localized and do not invade nearby tissues or organs.
102
what is cell migration
Cell migration is a complex process that involves the coordinated rearrangement of the cytoskeleton and the redistribution of integrin molecules at the cell surface.
103
What is the role of integrins in regulating cell migration, and how do they link the extracellular matrix to the cytoskeleton to facilitate this process
Integrins are cell surface receptors that mediate the attachment of cells to the extracellular matrix (ECM), and they play a critical role in regulating cell migration by providing a link between the ECM and the cytoskeleton.
104
How do the Rho GTPases Rho, Rac1, and Cdc42 regulate cytoskeletal rearrangements and integrin signaling during cell migration, and what is the role of actin filaments and focal adhesions in this process
The Rho GTPases Rho, Rac1, and Cdc42 are key regulators of cytoskeletal rearrangements and integrin signaling during cell migration. They help to control the formation of actin filaments, which provide the structural support for cell movement, and they also regulate the turnover of focal adhesions, which are specialized structures that link the ECM to the cytoskeleton.
105
How do the Rho GTPases promote cell migration and invasion, and what is the significance of these processes in the context of cancer progression
By promoting cytoskeletal rearrangements and integrin signaling, the Rho GTPases facilitate cell migration and invasion, which are critical processes in cancer progression.
106
What other stages of tumorigenesis, apart from cell migration, have the Rho GTPases been implicated in, and how do they contribute to the invasive and metastatic properties of cancer cells
In addition to their role in cell migration, the Rho GTPases have also been implicated in earlier stages of tumorigenesis, such as loss of epithelial cell polarity, disruption of the basal membrane, and increased proliferation. By stimulating motility and ECM degradation, the Rho GTPases can contribute to the invasive and metastatic properties of cancer cells, which are key factors in cancer progression and metastasis.
107
how can cancer cells partially degrade the extracellular matrix and what does this degradation facilitate
Cancer cells can partially degrade the extracellular matrix (ECM) by secreting matrix metalloproteases (MMPs), which are activated by integrins. This degradation of the ECM facilitates cancer cell invasion and metastasis, and also releases signaling molecules that promote tumor growth and angiogenesis
108
What is the process by which MMPs become activated, and how do cancer cells activate integrins to increase expression or maturation of MMPs
MMPs are secreted as inactive zymogens and require activation by proteolytic cleavage to become active. Cancer cells can activate several integrins, which are cell surface receptors that mediate adhesion to the ECM, leading to increased expression or enhanced maturation of MMPs.
109
what is the most important proteases in cancer cell invasion
The most important proteases in terms of cancer cell invasion are the matrix metalloproteases (MMPs). MMPs are zinc-dependent endopeptidases that are capable of degrading various components of the extracellular matrix (ECM), including the basement membrane and stromal matrices.
110
What are the different sources of MMPs in the tumor microenvironment
There are many different types of MMPs, some of which are secreted by tumor cells themselves, while others are induced in neighboring cells such as fibroblasts and macrophages
111
why do tissues contain TIMPs and what do they regulate and what happens if the balance is disrupted
To prevent excessive MMP activity, most tissues contain tissue inhibitors of MMPs (TIMPs), which can regulate the activity of MMPs and maintain normal levels of MMP activity. However, in cancer, the balance between MMPs and TIMPs is often disrupted, leading to increased MMP activity and ECM degradation.
112
What is the role of MMPs in cancer cell invasion and metastasis, and what are the implications of this process for cancer progression
The degradation of the ECM by MMPs is a critical step in cancer cell invasion and metastasis, as it allows cancer cells to move through the ECM and invade surrounding tissues.
113
How does the degradation of the ECM by MMPs promote tumor growth and angiogenesis, and what is the significance of these processes for cancer progression
In addition, the degradation of the ECM can release growth factors and other signaling molecules that promote tumor growth and angiogenesis, which is the formation of new blood vessels that supply nutrients to the tumor.
114
what a 5 different MMPs and what do they degrade
- Collagenase-1: degrades native collagen types I - III
- Gelatinase-A: degrades collagen type IV, gelatin, and elastin
- Gelatinase-B: degrades collagen type IV, gelatin, and elastin
- Stromelysin-1: degrades proteoglycans, laminin, collagen type IV, fibronectin, and gelatin
- Matrilysin: degrades proteoglycans, laminin, collagen type IV, fibronectin, and gelatin
115
How do cancer cells survive within the bloodstream and colonize distant organs, and what are some of the key factors that contribute to the formation of secondary tumors in the same organ despite different tissue origins
Cancer cells that have detached from the primary tumor must survive within the bloodstream, where they are exposed to shear forces that can prevent their attachment to the vessel walls. However, some cancer cells are able to survive these conditions and colonize distant organs by utilizing specific integrin-ligand interactions to attach to and invade the surrounding tissues. Once localized to the metastatic site, cancer cells may respond to local mitogenic stimuli and form secondary tumors in the same organ, despite their different tissue origins. This process is a critical step in the spread of cancer and can make the disease much more difficult to treat.
116
What are the stages involved in cell-cell contact formation, and how are strong mechanical connections achieved
Cell-cell contact formation involves distinct stages, characterized by changes in the organization of the actin cytoskeleton, molecular composition, and direction of forces. Cadherin binding initiates the process, which is mediated by β-catenin and α-catenin. As junctions mature, the actin cytoskeleton is organized into stress fibers, focal adhesions, and cortical actin networks. Stable cell-cell contacts require strong mechanical connections, achieved through adherens junctions and desmosomes.
117
what is the function of integrins and cadherins
Both integrins and cadherins play a crucial role in modulating the mechanical properties of cells and their microenvironment.
118
what do signaling events triggered by integrins and cadherins regulate
Signaling events triggered by integrins and cadherins regulate cytoskeletal dynamics, cell shape, and mechanical properties, enabling cells to respond to and adapt to changes in their environment.
119
what are some examples of cell surface receptors that bind to different matrix components,with examples of each receptor
- RGD receptors (α5β1, αVβ3, αVβ1,αVβ5, αVβ6, αVβ8, and αIIbβ3)
- Laminin receptors (α1β1, α2β1, α3β1, α6β1, α7β1, and α6β4)
- Leukocyte-specific receptors (αLβ2, αMβ2, αXβ2, and αDβ2)
- Collagen receptors (α1β1, α2β1, α3β1, α10β1, and α11β1)
120
what does ECM molecules include
ECM molecules include fibronectin, collagen, laminin, fibrinogen, thrombospondin, and glycoproteins such as tenascin C, osteopontin, and nefronectin.
121
what impacts the organisation of cell-ECM adhesion
Actin cytoskeleton architecture affects cell-ECM adhesion organization.
122
what connects actin cytoskeleton of cells to ECM
Integrins are transmembrane receptors that connect the actin cytoskeleton of cells to the extracellular matrix (ECM) by forming focal adhesions
123
What is the role of integrins in cell migration and how do they mediate adhesion to the extracellular matrix
Integrins are cell surface molecules that link the cytoskeleton to the cell membrane and mediate cell-matrix interactions. They consist of 18α and 8β subunits, which can form 24 different heterodimers. Integrin subunits have an extracellular domain, a transmembrane region, and a cytoplasmic domain. The cytoplasmic domains do not have kinase activity, but they participate in signal transduction by linking to other cytoplasmic kinases and adaptor molecules.
124
What is the structure of integrin heterodimers and what are the conserved sequences in their cytoplasmic domains that interact with each other
Integrin heterodimers have extracellular ligand binding sites and two leg regions that cross the cell membrane into the cytoplasm. The cytoplasmic domains of integrins have conserved sequences that interact with each other, including a GFFKR sequence in the α subunit and two NPxY sequences in the β subunit. The GFFKR sequence forms a salt bridge with the β subunit cytoplasmic domain when the integrin is inactive, and the NPxY sequences bind to adaptor molecules with phosphotyrosine-binding domains such as talin.
125
What are the different stages of carcinogenesis in which integrins are implicated
Integrins are implicated in multiple stages of carcinogenesis, including invasion, acquisition of transformed phenotype, migration, extracellular matrix remodeling, and metastasis.
126
What is the role of FAK in cancer cell invasion and how does it contribute to the formation of integrin-mediated focal adhesion-like structures with the extracellular matrix
Cancer cell invasion is a critical step in metastasis, requiring cells to disrupt cell-cell interactions, undergo cytoskeletal remodeling, and acquire migratory capabilities. This process involves activation of FAK, which helps to assemble dynamic integrin-mediated focal adhesion-like structures with the extracellular matrix (ECM).
127
What are the specialized cells that make up bone, and what are their roles in forming and maintaining bone tissue
Dense connective tissue includes cartilage and bone, both of which have important mechanical roles in the body. Cartilage is found in joints and provides a smooth surface for joint movement as well as shock absorption. Bone provides mechanical support and also serves as a storage site for calcium. Bone is composed of specialized cells called osteoblasts, osteocytes, and osteoclasts, which work together to form, grow, and maintain bones. Osteoblasts and osteocytes produce extracellular matrix and establish conditions for its calcification, while osteoclasts resorb and remodel bone as needed.
128
What are the characteristic features of loose connective tissue and what types of cells are present in this tissue and provide an example of a location where loose connective tissue can be found.
Sparse extracellular matrix of hyaluronan and
proteoglycans, few collagen and elastic fibrils.
Cell population: fibroblasts, both indigenous and
emigrant connective tissue cells, lymphocytes,
plasma cells, macrophages, eosinophils,
neutrophils, mast cells and fat cells.
Example: The loose connective tissue
underlying the epithelium in the gastrointestinal
tract
129
what is cartlage, here is it found and what are chondrocytes and what do they secrete
cartilage is a type of connective tissue that plays a mechanical role and is found in body parts such as the nose and ears. In sharks, cartilage forms the entire skeleton. Chondrocytes are cells that are found within cartilage and secrete molecules that make up the cartilage matrix.
130
what is endochondral ossification
The formation of a long bone by replacement of cartilage is a process called endochondral ossification.
131
what is bone formation
Bone formation, also known as ossification, is the process of building new bone tissue.
132
How does the plant extracellular matrix influence plant development and cell division
Plant extracellular matrix provides mechanical support to the plant cell wall made of cellulose, other polysaccharides, and glycoproteins. This matrix also influences plant development and cell division. The plant cell junctions are formed by plasmodesmata, which are channels that allow for communication and transport of molecules between adjacent plant cells.
