Cell Junction, Cell adhesions & Extracellular Matrix (Sept. 9-Denning) Flashcards

1
Q

List the 2 main types of tissue involved in cell junctions

A

1) Epithelial tissue

2) Connective tissue

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2
Q

What are the characteristics of epithelial tissue

A
  • Low ECM & High # cells
  • Cells are tightly bound together in sheets
  • Cells bear most of the mechanical stress through junctional complexes that attach to the cytoskeleton.
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3
Q

List the characteristics of connective tissue

A
  • High ECM & Low # of cells
  • Matrix is rich in fibrous polymers (e.g., collagen)
  • Matrix bears most mechanical stress
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4
Q

List the 5 main types of cellular junctions and their particular functions

A

1) Occluding: Seal cells so nothing can pass in between (tight junctions)
2) Cell-Cell Anchoring: Connects lateral walls of cells together (Actin & Adherens/IFs & desmosomes)
3) Channel-Forming: Allows selective transport of materials between cells (gap junctions)
4) Cell-Matrix Anchoring: Links together cell and ECM (actin/focal adhesions or hemidesmosomes/IFs)
5) Signal-Relaying junctions: Neurotransmitter secretions

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5
Q

Describe the function of claudins and occludins in tight junctions

A
  • Claudins are 4-pass transmembrane proteins.
  • Found at lateral surface just below apical surface of cell.
  • Prevent paracellular transport
  • Occludins serve similar function, but are found in significantly less number
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6
Q

T/F: Glucose can normally pass between epithelial cells of the intestine

A

False: tight junctions prevent leaking and transportation of molecules between cells. Glucose uses Na+ symporter to move and undergo transcellular transport

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7
Q

What is the function of anchoring junctions?

A
  • Stabilize cells against mechanical stress

- Mechanically attach cells and their cytoskeleton to their neighbors or to the extracellular matrix

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8
Q

For the 4 subtypes of anchoring proteins, list the (1) type, (2) transmembrane adhesion protein, (3) cytoskeletal attachments

A

1) Adherens (cell-cell) - cadherin - actin
2) Desmosome (Cell-cell) - cadherin (desmoglein) - IF
3) Focal adhesions (Cell-matrix) - integrin - actin
4) hemidesmosomes (cell-matrix) - integrin - IF

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9
Q

What is the function of cadherin?

A

Cadherins are transmembrane adhesion proteins that work to form cell-cell junctions between filaments via anchor proteins

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10
Q

What is the adhesion belt in adherens junctions?

A

Join an actin bundle in one cell to actin bundle in adjacent cell
Form adhesive belt just below tight junction

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11
Q

What ion does cadherin require for assembly?

A

Ca2+

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12
Q

Where are desmosomes typically found?

A

Between cells. They function as “spot welds”

They are anchored to IFs via desmosomal cadherins and plaque proteins

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13
Q

What are the functions of focal adhesions?

A
  • Link the cell to ECM

- Allows cell to hang on to surroundings (think leucocyte rolling)

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14
Q
Focal adhesions bind to \_\_\_\_ via the transmembrane protein \_\_\_\_\_\_
(A) actin; integrin
(B) microtubules; integrin
(C) intermediate filaments; cadherin
(D) desmosomes; actin
A

(A) Focal adhesions are connected to actin via anchoring proteins and use integrins (transmembrane ECM binding proteins) as the interacting subunits

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15
Q

List the (1) function, (2) transmembrane protein that mediates the connection, and (3) the final end connection of hemidesmosomes

A

1) Distribute forces on an epithelium to the basal lamina
2) Integrins mediate basal lamina adhesion
3) Anchor proteins link integrins to intermediate filaments

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16
Q

Describe the phenomenon that is cadherin dependent sorting?

A

Homophilic binding of cadherin dimers favors association of like cadherin dimers. This binding allows the eventual separation and distinct cell types aggregating together which allow tissue homeostasis and sorting of similar cell types

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17
Q

What are selectins?

A

Selectins are Lectins: Carbohydrate binding proteins
They are transient, calcium-dependent adhesion molecules
which exhibit heterophilic binding and are connected to integrins

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18
Q

Elaborate on the phenomenon that is leukocyte rolling in the bloodstream following an injury. What are the functions of selectins and integrins in this interaction?

A
  • Injury causes release of cytokines…Cytokines cause surface proteins to display selectins cause carbohydrates to stick (typically found on surface of WBC)
  • Transient low affinity, low strength with SELECTINS to WBC
  • Integrins cause a stronger adhesion when finally recognized and allow import of WBC into cell through endothelium.
19
Q

What are communicating gap junctions?

A
  • Electrically couple adjacent cells and small molecules such as ions, and nucleotides can pass through.
  • Important for heart muscles to allow things like Ca2+ to move through and equilibrate the spike throughout all cells to give unified contraction.
  • Cells that are diferent from each other (not specialized cells will not be coupled)
20
Q

Describe the structure of connexins and how they relate to the formation of gap junctions

A

Gap junctions are formed by connexins :
-4 pass transmembrane proteins
-6 connexins form a functional pore: Connexon
-Permeability varies with connexin composition

21
Q

Discuss the function of scaffold proteins in synaptic junctions

A

Scaffold proteins organize adhesive proteins, ion channels, receptors and other vesicle-docking proteins to relay signals across a synapse (neurons).

22
Q

The ECM is a hydrated gelatinous material that is made up of these 3 components…

A

Glycosaminoglycans, proteoglycans, and fibrous proteins.

23
Q

Cells which secrete ECM include…

List 4

A

1) Fibroblasts
2) Chondroblasts (cartilage)
3) Osteoblasts (bone)
4) Epithelium (basal lamina)

24
Q

What type of tissue is ECM prevalent in?

A

Connective tissue

25
Q

1) This tissue type uses matrix to bear mechanical stress…

2) This tissue type absorbs mechanical stress through cellular junctional complexes that attach to the cytoskeleton

A

1) Connective tissue

2) Epithelial tissue

26
Q

Describe 3 characteristics of Glycosaminoglycans (GAGs)

A
  1. One sugar is an amino sugar (Sulfated and bears (-) charge)
  2. Other sugar is a ironic acid (glucoronic or iduronic…Coo- group)
  3. polysaccharides are stiff and absorb large amounts of water: occupy space
27
Q

Hyaluronan (hyaulorinic acid or hyaluronate):
(A) contains sulfated sugars
(B) is composed of complex GAG consisting of more than 25,000 disaccharide units
(C) not attached to protein and is synthesized at plasma membrane
(D) Is not resistant to compressive forces in joints and tissues
(E) Both A and D

A

(C) Hyaluronan is simplest GAG of up to 25,000 disaccharide units. It is a space filler through which cells migrate in ECM and resists compressive forces

28
Q

How are proteoglycans different from glycosaminoglycans?

Do they differ from glycoproteins?

A

Proteoglycans are composed of a core protein to which GAG is covalently attached.

Unlike glycoproteins, proteoglycans are highly carbohydrate like in composition (95% by weight) and contain at least 1 GAG

29
Q

What is the difference between glycoproteins and proteoglycans?

A

Glycoproteins have short, branched side chains and are mostly protein in composition; while proteoglycans usually contain long unbranched side chains and are mostly carbohydrate in composition.

30
Q

What are the functions of proteoglycans?

A
  1. regulation of molecular and cellular movement (gels)

2. chemical signaling between cells - binding of growth factors, protease…

31
Q

What are the main characteristics of collagens protein in ECM

A
  1. Long, stiff triple alpha helix
  2. Gly - proline - hydroxyproline repeating sequences
  3. Hydroxyproline and hydroxylysine form interchain H-bonds…stabilize triple helix
  4. Highly cross link through lysine aldehydes
  5. primarily responsible for strength of ECM
32
Q

What are the two genetic collagen disorders we have discussed in class?

A
  1. osteogenesis imperfecta: Type I collagen defect with autosomal dominant inheritance. Leads to increased bone fractures and skeletal abnormalities
  2. Ehlers-Danlos syndrome: Mutations in Type I, II, V collagen. decreased collagen hydroxylation. Autosomal dominant inheritance. Leads to skin hyper-extensibility, joint dislocation, hyper mobility, vessel weakness
33
Q

What is the function of elastin?

A

Imparts elasticity and flexibility to tissues

34
Q

Marfan’s syndrome is a mutation in the fibrillin sheath of elastic fibers. It is autosomal dominant disease characterized by which one or more of the following symptoms:

a) excessive growth of long bones
b) short stature
c) normal cartilage and ligaments
d) weakened blood vessels, hear valves

A

Both (a) and (d)

Alos causes: Aortic dilation/rupture, tall stature, weakened blood vessels, malformed cartilage and ligaments

35
Q

What is the function of fibronectin?

A

Adhesive glycoprotein that binds cells to matrix and guides cell migration

36
Q

Fibronectin binds to (1) ______ to attach to the ECM. It does this via a triplet amino acid (2) ______ interaction

A

(1) integrins

2) RGD (Arg-Gly-Asp

37
Q

List the 5 main functions of the basal lamina

A
  1. molecular filter
  2. barrier for cell migration &
  3. cell migration
  4. cell orientation
  5. cell survival
38
Q

What are the 2 main components of the basal lamina

A
  1. Laminin - adhesive protein that binds cells to the basal lamina
  2. Type IV collagen
39
Q

True/False: The basal lamina allows for regeneration of nerves and acetylcholine receptors at the site of original junction in degenerated muscle and nerve experiments

A

True. Basal lamina allows proper orientation and regeneration as long as residual shell of residual basal lamina is left intact

40
Q

Describe the main characteristics of integrins (list of 5)

A
  1. heterodimer of alpha and beta glycoproteins
  2. overlapping specificity - multiple integrins can bind fibronectin or laminin (ECM matrix proteins)
  3. Linked to actin cytoskeleton
  4. Matrix receptors
  5. Low affinity, high copy number
41
Q

What are the two adaptor proteins that are used to anchor integrins with actin filaments?

A

Vinculin and talin

42
Q

Describe inside-out signaling regulation of integrins

A
  • Inactive integrins are activated by the cells
  • Strong talin binding
  • Bind antigen presenting cell pr can cause aggregation
43
Q

Descibe outside-in signaling regulation of integrins

A
  • clustering of integrins at ECM contact sites activates signaling
  • characterized by strong ligand binding on outside of cell
  • focal adhesion kinase (FAK) is recruited and activated
  • Similar to conventional GF receptors