Cell Junctions, Cell Adhesion, and the Extracellular Matrix 1 & 2 Flashcards
1
Q
How do cells form a massive and strong structure?
A
- Use the strength of the extracellular matrix.
- Use the strength of the cytoskeleton inside the cells and on cell-cell adhesions that tie the cytoskeleton of heighboring cells together.
2
Q
Attachments to other cells and to extracellular matrix control the orientation of each cell’s what?
A
internal structure
3
Q
What do cell-cell juctions provide for cells?
A
Provide communication, allowing cells to coordinate their behavior and regulate the gene expression.
4
Q
What are the two main ways to connect animal cells and provide strength?
A
> Connective Tissue - such as bone or tendon, extracellular matrix is plentiful and cells are sparsely distributed within it.
> Epithelial Tissue - the cytoskeleton of cells is linked from cell to cell by anchoring junctions and the extracellular matrix is scanty, consisting mainly of a thin mat called the basal lamina.
Cell-matrix attachments bond epithelial tissue to the connective tissue beneath it
5
Q
What are the 4 functional classes of cell junctions?
A
- Anchoring Junctions
- Occluding Junctions
- Channel-Forming Junctions
- Signal-Relaying Junctions
6
Q
What are anchoring junctions?
A
Cell-cell adhesions and cell-matrix adhesion, and are connected to cytoskeletal filaments inside the cell.
7
Q
What are occluding junctions?
A
Seal gaps between epithelial cells so as to make the epithelial sheet into an impermeable barrier.
8
Q
What are channel-forming junctions?
A
Create passageways for small molecules and ions to pass from cell to cell.
9
Q
What are signal-relaying junctions?
A
Allow signals to be relayed from cell to cell across their plasma membranes at cell-to-cell contact.
10
Q
What are the two anchoring junctions that are found at actin filament attachment sites?
A
- Cell-cell junctions (adherens junctions)
- Cell-matrix junctions (actin-linked cell-matrix adhesions)
11
Q
What are the two anchoring junctions that are found at intermediate filament attachment sites?
A
- Cell-cell junctions (desmosomes)
- Cell-matrix junctions (hemidesmosomes)
12
Q
What are the two different types of occluding junctions?
A
- tight junctions (in vertebrates)
- septate junctions (in invertebrates)
13
Q
What do tight junctions do?
A
Seals gap between epithelial cells.
14
Q
What type of junction are tight junctions?
A
occluding junction
15
Q
What do adherens junctions do?
A
Connects actin filament bundle in one cell with that in the next cell.
16
Q
What do desmosomes do?
A
Connects intermediate filaments in one cell to those in the next cell.
17
Q
What type of cell junction are adherens junctions and desmosomes?
A
cell-cell anchoring junctions
18
Q
What do gap junctions do?
A
Allow the passage of small water-soluble molecules from cell to cell.
19
Q
What type of cell junction are gap junctions?
A
channel-forming junctions
20
Q
What do hemidesmosomes do?
A
Anchor intermediate filaments in a cell to extracellular matrix.
21
Q
What do actin-linked cell-matrix adhesions do?
A
Anchors actin filaments in cell to extracellular matrix.
22
Q
What type of cell junction are actin-linked cell-matrix adhesion anchors and hemidesmosomes?
A
cell-matrix anchoring junctions
23
Q
What do transmembrane adhesion proteins mediate?
A
Anchoring Junctions
24
Q
What do transmembrane adhesion proteins play a major role in?
A
Anchoring Junctions
25
What are transmembrane adhesion proteins?
Span the membrane, with on end linking to cytoskeleton inside the cell and the other end linking to other structures outside the cell.
26
What are the two families of transmembrane adhesion proteins?
- Cadherin -> mediating cell-cell connection.
| - Integrin -> mediating attachment of cells to matrix.
27
What are the two other adhesion superfamilies of cell-cell adhesion molecules?
- Selectin
| - Immunoglobulin (Ig)-superfamily
28
What cell-cell junction protein has cadherin (classical cadherin) as its transmembrane adhesion protein and actin filaments as its intracellular cytoskeletal attachment?
adherens junction
29
What cell-cell junction protein has cadherin (nonclassical) as its transmembrane adhesion protein and intermediate filaments as its intracellular cytoskeletal attachment?
desmosome
30
What is the transmembrane adhesion protein for the two cell-matrix junction proteins, actin-linked cell-matrix adhesion and hemidesmosome?
integrin
31
What cell-matrix junction protein binds to actin filaments as its intracellular cytoskeletal attachment?
actin-linked cell-matrix adhesion
32
What cell-matrix junction protein binds to intermediate filaments as its intracellular cytoskeletal attachment?
hemidesmosome
33
Which cell-cell junctions are cadherins the principal component for?
- adherens juctions
| - desmosomes
34
What are the two cadherin superfamilies?
- classical cadherins
| - nonclassical cadherins
35
What are classical cadherins?
Are the main mediators of Ca2+-dependent adherens junctions.
36
What are nonclassical cadherins?
Include desmocollins and desmogleins that form desmosome junctions, and the recently discovered large subfamily of protocadherins, which are implicated in neuronal plasticity.
37
List some examples of classical cadherins.
E-cadherin (epithelial cells and brain)
N-cadherins (muscle, nerve, lens cells, and fibroblasts)
VE-cadherin (endothelial cell)
P-cadherin (placenta and epidermis)
38
What do cadherin protein mediate?
Ca2+-dependent cell-cell adhesion.
39
What does the extracellular portions of cadherin superfamily proteins contain?
Multiple copies of the cadherin domain motif.
40
You know that the extracellular portions of cadherin superfamily protein are the same, but why are the intracellular portions varied?
So they are able to interact with different intracellular ligands and components that anchor the cadherin to the cytoskeleton.
41
Is binding between cadherins generally homophilic or heterophilic?
Homophilic
42
True of False:
The spacing between the cell membranes at an anchoring junction is precisely defined.
True
43
Each cadherin domain forms a rigid unit, joined by the next cadherin domain by a hinge. What binds to sites near each hinge and prevents it from flexing?
Ca2+ ions
44
What happens to the the structure of linked cadherin domains if Ca2+ is removed?
The hinges can flex, and the structure becomes floppy. At the same time, the conformation at the N terminus changes, weakening the binding affinity and disrupting the adhesion.
Cadherins are then degraded.
45
Do cadherins typically bind to their partners with relatively low or high affinity?
Low Affinity
46
Since cadherins typically bind to their partners with low affinity, how are strong attachments made?
Strong attachments result from the formation of many weak bonds in parallel, functioning like Velcro to hold cells together.
47
Via what interaction are cadherins able to be clustered side-by-side on the same cell?
Interactions between their N-terminal head regions, and via their attachments of their intracellular tails to other anchoring proteins.
*adhesion is strong but can be easily disassembled*
48
You know that cadherin-dependent homophilic adhesions mediate highly selective recognition, but what does this enable the cells to do?
Enables cells of a similar type to stick together and to stay segregated from other types of cells (sorting out).
49
In the functions of cadherin-mediated adhesion, what is sorting out?
Cadherin-dependent homophilic adhesions mediate highly selective recognition, enabling cells of a similar type to stick together and to stay segregated from other types of cells - called sorting out.
50
During development, what does the changing patterns of expression of cadherins determine?
Selective assortments of cells.
*Appearance and disappearance of cadherins correlate with major morphogenetic events in which tissues segregate from one another.*
51
What do intracellular anchor proteins do?
Link classical cadherins to cytoskeleton.
52
What protein links classical cadherins to the cytoskeleton?
intracellular anchor proteins
53
List three types of anchor proteins?
> Beta-catenin
> p120-catenin
> gamma-catenin (plakoglobin)
54
What are adherens junctions an essential part of?
The machinery for modeling the shape of multicellular structures.
55
In what type of tissue are adherens junctions primarily present in?
epithelia
56
What do adherins junctions often form?
Continuous adhesion belt (or zonula adherens) close beneath the apical face of the epithelium, encircling each of the interacting cells in the sheet.
57
Within each cell, what lies adjacent to the adhesion belt, oriented parallel to the plasma membrane and tethered to it by the cadherins and their associated intracellular anchor proteins?
a contractile bundle of actin filaments
58
# Fill in the blank:
Desmosome junctions are structurally similar to adherens junctions but link to _____ _____.
intermediate filaments
*NOTE: adherens junctions attach to actin filaments*
59
What do desmosomes provide?
mechanical strength
**Bundle of intermediate filaments that are anchored to the desmosomes form a structural framework of great tensile strength**
**Appear as button like spots of intercellular adhesion, riveting the cells together.**
60
What is the structure of a desmosome?
> On the cytoplasmic surface is a dense plaque composed of different anchor proteins.
> A bundle of keratin intermediate filaments is attached to the surface of each plaque.
> Proteins of cadherin family bind to the plaques and interacts through their extracellular domains to hold the adjacent membranes together by a Ca2+-dependent mechanism.
61
What are the desmosomal cadherins that undergo homophilic and heterophilic binding?
- desmoglein
| - desmocollin
62
What do the cytoplasmic tails of desmoglein and desmocollin bind to?
Plakoglobin (gamma-catenin) and plakophilin, which in turn bind to desmoplakin.
63
What protein binds to the sides of intermediate filaments, thereby tying the desmosome to these filaments?
desmoplakin
64
What is the ODP and IDP?
outer dense plaque
inner dense plaque
**talking about desmosomes**
65
How are intermediate filament networks of adjacent cells indirectly connected to one another?
Through desmosomes and to the basal lamina through hemidesmosomes.
66
What type of intermediate filaments attach to desmosomes in most epithelial cells?
keratin filaments
67
What missense mutation leads to arrhythmogenic right ventricular cardiomyopathy (ARVC)?
missense mutations in Desmocollin-2
68
What are the 4 types of cell junctions?
> anchoring junctions (cell-cell anchoring adhesions and cell-matrix adhesions)
> occluding junctions
> channel-forming junctions
> signal-relaying junctions
69
What are the 4 transmembrane adhesion proteins?
> cadherin
> intergrins
> selectins
> immunoglobulin-superfamily
70
What cell junction are cadherins a crucial component in?
adherens junctions and desmosomes
71
What are the characteristics of cadherin-mediated cell-cell adhesion?
> homophilic interaction
> involvement of Ca2+
> clustering
72
What are tight junctions?
Occluding junctions found in epithelia and endothelial sheet.
73
List the functions of tight junctions.
- form a seal between cells
- forma a fence between membrane domains
- recruit cytoskeleton as well as signaling molecules at their cytoplasmic side
74
What are the two main tight junction proteins?
- claudin (the main functional component)
| - occludin
75
True or False:
Each sealing strand of tight junction is composed of a long row of 4 pass transmembrane adhesion proteins embedded in each of the two interacting plasma membranes.
True
76
What is the main transmembrane protein in tight junctions?
claudin
77
What does the protein Tip (tight junction protein), aka - ZO protein, do?
ZO anchors tight junctions to actin cytoskeleton.
78
What are the 3 functions of tight junctions?
> Barrier function
> Fence function
> Signaling function
79
What conserved polarity protein complexes control polarization processes and maintain polarity?
> Par (partitioning defective)
> Crumbs
> Scribble
80
What does the establishment of epithelial cell-cell contacts and the subsequent apico-basal polarization require?
E-cadherin-mediated cell-cell adhesion
81
True or False:
Each gap junction can contain a cluster of a few to many thousands of connexons and each gap-junctional plaque can readily assemble or disassemble.
True
82
True or False:
New connexons are continually added around the periphery of an exciting junctional plaque, while old ones are removed and destroyed.
True
83
How are new connexons inserted into the plasma membrane?
By exocytosis, and then diffuse in the plane of the membrane until they meet the periphery of a plaque and become trapped.
84
What are the two families of channel-forming proteins that span gap junctions?
- Connexins (predominant form)
| - Innexins
85
What do the channel forming proteins of gap junctions, connexins and innexins, allow?
Inorganic ions and other small water-soluble molecules to pass directly from the cytoplasm of one cell to another, thereby coupling the cells both electrically and metabolically.
**have to be less than 1000 daltons**
86
True of False:
The hemichannel connexons are hexameric: they consist of 6 connexin protein subunits.
True
**connexins are four-pass transmembrane proteins**
87
True of False:
A connexon may be made of the same (homohexameric) or different (heterohexameric) subunits.
True
88
Do individual gap-junction channels remain continuously open?
No, instead, they flip between open and closed states.
89
What happens to a cell when it is damaged?
Its plasma membrane can become leaky.
90
What happens to a cell when its plasma membrane becomes leaky after being damaged?
Ca2+ ions present at high concentration in the extracellular fluid then move into the cell, and valuable meatbolites leak out.
**if the cell were to remain coupled to its healthy neighbors, these too would suffer a dangerous disturbance of their internal chemistry - this is why it is good that a large influx of calcium causes the gap-junctions to close immediately. Thus, isolating the cell and preventing the damage from spreading to other cells.
91
What is the basal lamina (basement membrane)?
> underlies all epithelia
> surrounds individual muscle cells, fat cells, and Schwann cells
> the basal lamina separates these cells and epithelia from the underlying or surrounding connective tissue and forms the mechanical connection between them
> in kidney glomerulus, a basal lamina lies between two cell sheets and functions as a selective filter
92
What are the functions of the basal lamina?
- Separating cells from the underlying or surrounding connective tissue.
- A selective filter.
- Determine cell polarity.
- Influence metabolism.
- Organize the proteins in adjacent plasma membrane.
- Promotes cell survival, proliferating or differentiation.
- Serve as solid surface for cell migration.
93
What are the two main classes of extracellular macromolecules that the lamina consists of?
- Fibrous protein (usually glycoproteins)
| - Glycosaminoglycan (GAG)
94
What are the components of the lamina?
> laminin
> type IV collagen
> nidogen
> proteoglycan perlecan
95
True of False:
The laminin is the primary organizer of the sheet structure of the basal membrane.
True
96
What are the characteristics of laminin-1 (classical laminin)?
> a large, flexible, multidomain glycoprotein
> composed of three polypeptides (alpha, beta, gamma) held together by disulfide bonds
- the alpha, beta, and gamma chains are arranged in the shape of an asymmetric bouquet, like a bunch of three flowers whose stems are twisted together at the foot but their heads remain separate.
97
What provides tensile strength to the basal lamina?
type IV collagen
98
What do nidogen and perlecan serve as in the basal lamina?
Serve as linker to connect the laminin and type IV collagen networks once the laminin is in place.
99
Which two transmembrane receptors organize the basal lamina assembly?
> integrin
| > dystroglycan
100
List 3 diverse functions of the basal lamina?
> thick basal lamina in the kidney glomerulus acts as one of the layers of molecular filter
> basal lamina acts as a selective barrier to the movement of cells
> basal lamina is important in tissue regeneration after injury
101
List the transmembrane proteins in tight junctions?
> claudin
> occludin
> junctional adhesion molecules
102
What are the three functions of transmembrane proteins in tight junctions?
> barrier
> fence
> signaling transduction
103
What are the 3 polarity protein complexes?
> Par
> Crumbs
> Scribble
104
What is the predominant form of gap junction protein?
connexin
105
What does an integrin molecule consist of?
Two noncovalently associated subunits, alpha and beta.
106
True or False:
alpha and beta subunits both span the cell membrane with short C-terminal tails and large N-terminal extra-cellular domains.
True
107
What do the head, or N-terminal domain, of integrin dimer directly bind to?
Extracellular matrix proteins and a variety of ligands.
108
What does the intracellular tail of the beta subunit bind to?
A complex of proteins that form a linkage to cytoskeleton.
109
Which protein mediates the intracellular linkage to actin in integrin?
talin
110
What are the most prominent cell-matrix attachment sites in epithelia?
hemidesmosomes - where the specific type of integrin (alpha6beta4) anchors the cells to laminin in the basal membrane
111
What can cause a blistering disease of the skin?
defects in any of the proteins involved in hemisesmosomes attachment.
112
What is under allosteric regulation when talking about integrins?
As an integrin binds to or detaches from its ligands, it undergoes conformational changes that affect both the intracellular and the extracellular ends of the molecule.
113
How do integrins appear in the absence of an extracellular ligand?
Integrins appear as tightly folded V-shaped molecules.
114
What do integrins do in the presence of a ligand?
Unfold into an extended structure with two straight and separated legs.
115
What are focal contacts when talking ligand-bound integrins?
Focal contacts are the sites that the extracellular matrix, integrins and the cell cytoskeleton interact.
116
Conformation change of integrin - inside-out activation by intracellular molecules.
> Intracellular molecules, including PIP2, promote the translocation of talin to integrin beta cytoplasmic tails.
> Talin competes with the integrin alpha chain for its binding site on the tail of the beta chain.
> When talin binds to the beta chain it breaks alpha-beta linkage, allowing two legs of the integrin into its extended, active conformation.
> Integrin activation increases the affinity of individual integrins for extracellular matrix ligands.
117
How do integrins signal?
Bidirectionally - that is, not only can information flow from extracellular stimuli to induce intracellular changes (outside-in signaling), but intracellular stimuli can also cause extracellular changes (inside-out signaling).
118
What are focal adhesions?
Cellular structures that link the extracellular matrix on the outside of the cell, through integrin receptors, to the actin cytoskeleton inside the cell.
119
What is one of the major tyrosine-phosphorylated proteins found at focal adhesions?
FAK - a cytoplasmic protein tyrosine kinase
120
Which two main classes of extracellular macromolecules make up the matrix?
- Glycosaminoglycans (GAGs)
| - Fibrous proteins
121
What do proteoglycan molecules in connective tissue form?
A highly hydrated, gel-like "ground substance" in which the fibrous proteins are embedded.
122
Proteoglycan synthesis.
> sugars are added to the protein one at a time, with UDP-sugars serving as the prescursors.
> Initially a xylose residue is added to a serine in the protein.
> then two galactose residues are added, followed by a glucuronic acid (GlcUA) and an N-acetylglucosamine (GalNAc).
123
Why do GAGs tend to adopt highly extended conformations that occupy a huge volume relative to their mass?
Polysaccharide chains are too stiff to fold up into the compact structures and they are strongly hydrophilic.
124
How do GAGs help the cell to withstand compressive forces?
Their high density of negative charges attracts lots of cations, most notably Na+, that are osmotically active, causing large amounts of water to be sucked into the matrix. This creates a swelling pressure, that enables the matrix to withstand compressive forces.
125
What does proline do to the structure of collagens?
The ring structure of proline stabilizes the helical conformation in each alpha-chain.
126
How is collagen structured?
The alpha chain is arranged as a left-handed helix, with 3 amino acid per turn, and with glycine as every third amino acid.
127
Collagen Assembly.
> After being secreted into the extracellular space, collagen molecules assemble into higher-order polymers called collagen fibrils, which are thin structures.
> Formation of covalent cross-linked between lysine residues of the constituent collage molecules occurs to strengthen the fibrils.
> Collagen fibrils often aggregate into larger, cablelike bundles, several micrometers in diameter, which can be seen in the light microscope as collage fibers.
128
What are the co-factors of prolyl/lysyl hydroxylases?
> ascorbate
| > Fe2+
129
Which enzyme is defective in Ehlers-Danlos VI?
lysyl hydroxylase
130
Which enzyme is defective in Scurvy?
Prolyl Hydroxylase
