Cell Adhesion (Exam III) Flashcards
1
Q
What are tight junctions are categorized as
A
Occluding junctions
2
Q
Seals gaps between epithelial cells
A
Tight junctions
3
Q
Restricts the flow of substances between cells and forces them to go through the cell
A
4
Q
What type of junctions are cell-cell anchoring junctions
A
Adherens
Desmosomes
5
Q
Connect the actin filament bundles inside of one cell to the next
A
Aderens
6
Q
Connects intermediate filaments in one cell to those in the next cell
A
Desmosome
7
Q
A gap junction is categorized as what type of junction
A
Channel-forming junction
8
Q
Allows the passage of small water-soluble molecules from cell to cell
A
Gap junctions
9
Q
What are our types of cell matrix anchoring junctions
A
- Actin-linked cell matrix adhesion anchors
- Hemidesmosomes
10
Q
Connects/anchors actin filaments inside the cell to the extracellular matrix
A
Actin-linked cell matrix adhesion anchor
11
Q
Anchors intermediate filaments inside the cell to the extracellular matrix
A
Hemidesmosome
12
Q
What are the aderens junctions transmembrane adhesion protein
A
Cadherins
13
Q
What are the desmosomes transmembrane adhesion proteins
A
Cadherins
14
Q
Actin-linked cell-matrix adhesion anchors use what type of transmembrane protein
A
Integrin
15
Q
Hemidesmosomes use what type of transmembrane adhesion protein?
A
Integrin and collagen
16
Q
We have junctions that connect _____ to _____ and also junctions that connect _____ to ______
A
Cells to cells
Cells to ECM basement membrane
17
Q
What cellular junctions involve the ECM?
A
- Actin-linked cell matrix adhesion anchors
- Hemidesmosomes
18
Q
What cell junctions involve cell-cell connections?
A
- Tight junctions
- Adherens
- Desmosomes
- Gap junctions
19
Q
How many general principles of cell adhesion
A
6
20
Q
Principle 1: How do cells define there capacity for adhesion?
A
By selectively expressing certain plasma membrane receptors
21
Q
When cells define their capacity for adhesion, they selectively express certain plasma membrane receptors, what are these receptors?
A
CAMs (cell adhesion molecules)
22
Q
CAMs generally have:
A
Limited ligand-binding activity
23
Q
Generally cells expressing the proper mix of receptors is part of a genetic program for the:
A
Differentiation of the cell
24
Q
The 2nd principle: Many adhesion proteins bind ____ and many ligands bind _____
A
One main ligand; a single type of receptor
25
In accordance to the one-to-one rule for adhesion proteins binding one main ligand, or ligands binding a single receptor, there are many:
Exceptions to this rule
26
What is an example of an exception to the one-to-one binding rule of the second principle of adhesion?
Integrin family of receptors
27
The integrin family of receptors generally bind:
More than one ligand
28
Some ligands such as fibronectin bind
More than one integrin
29
Family of cellular adhesion molecules that prefer to bind themselves (they promote the adhesion of like cells)
Cadherins
30
When a cell adhesion molecules binds itself promoting the adhesion of like cells is an example of what type of interaction
Homophilic
31
Association of like receptors on two cells
Homophilic interaction
32
Cadherins require
Calcium
33
What do selectins bind?
Anionic polysaccharides
34
Selectins generally bring:
Two different cell types together
35
What would bind an anionic polysaccharide like those on mucins?
Selectin
36
What do most Ig-CAMs bind?
Other cell surface adhesion proteins
37
Association of unlike receptors on two cells
Heterophilic interaction
38
Ig-CAMs display what type of binding interactions?
Heterophilic interactions
39
Cadherins are associated with _____ interactions, while Ig-CAMs are associated with ____ interactions
Homophilic; Heterophilic
40
What type of cellular adhesion molecules bind a variety of ligands and ECM molecules
Integrins
41
Examples of a ECM molecule that integrin may bind
Fibronectin, laminin
42
A soluble protein that integrin may bind
Fibrinogen
43
Soluble protein that circulates in the blood and functions in the clotting pathway
Fibrinogen
44
Transmembrane protein associated with adherens junctions
Classical cadherin
45
Extracellular ligand adherens junctions bind to
Cadherin in the neighboring cell
46
Intracellular cytoskeletal attachment involved in adherens junctions
Actin filaments
47
Adherens junctions and desmosomes are both
Cell-cell junctions
48
Transmembrane adhesion proteins associated with desmosomes
Cadherin (desmoglein, desmocollin)
49
Extracellular ligand associated with desmosomes
Desmoglein and desmocollin in neighboring cell
50
Intracellular cytoskeletal attachment of desmosomes
Intermediate filaments
51
Actin-linked cell-matrix adhesion molecules and hemidesmosomes are both
Cell-matrix junctions
52
Transmembrane adhesion protein associated with actin-linked cell-matrix adhesion junctions
Integrin
53
Extracellular ligand associated with actin-linked cell matrix adhesion
Extracellular matrix proteins
54
Intracellular cytoskeletal attachment of actin-linked cell-matrix adhesion junctions
Actin filaments
55
Transmembrane adhesion protein associated with hemidesmosomes
Integrin, collagen
56
Extracellular ligand associated with hemidesmosomes
Extracellular matrix proteins
57
intracellular cytoskeleton attachment of hemidesmosomes
Intermediate filaments
58
Generally speaking anchoring proteins do not directly bind to the intracellular filaments bit they do so through:
Recruitments of anchoring filaments
59
Third principle: how do cells modulate adhesion?
1. Controlling surface density of adhesion receptors
2. Controlling state of aggregation of adhesion receptors
3. Controlling state of activation of adhesion receptors
60
Reflects not only the level of synthesis but also the portion of adhesion molecules between the plasma membrane and intracellular storage compartments
Surface density
61
An example of cells modulating surface density, state of aggregation and state of acitvation of their adhesion receptors is:
Endothelial cells expressing P-selectin
62
What do cadherins control?
The selective assortment of cells
63
Cells can sort themselves out according to _____ and ____ of the cadherins they express
Type; level
64
Cells can separate out based on the _____ of the cadherins they express
Density
65
Calcium-dependent adhesion molecules
Cadherins
66
What are cadherins critical for?
Establishing and maintaining intercellular connections
67
Cadherins appear to be crucial to the:
Spatial segregation of cell types
68
How are cadherins anchored into the cell?
Catenins
69
The anchoring complex of proteins of cadherins
Catenins
70
The cadherin-catenin complex forms the ______ junctions that connect epithelial cells together
Classic adherens junctions
71
What do catenins bind to in the cytoskeleton of the cell?
Actin
72
What is the cadherin bridge dependent upon?
Calcium
73
The fourth principle of adhesion: The rates of ____ and ____ are important determinants of cellular adhesion
Ligand binding; dissociation
74
When a cell surface adhesion protein binds their ligands weakly this allows for:
Rapidly reversible interactions
75
When multiple weak interactions cluster together to stabilize the adherens and desmosomes junctions- the combined strength of these bonds is said to increase the:
Avidity of the interaction
76
Strength of interaction
Avidity
77
Fifth principle of adhesion: What do many adhesion receptors interact with inside the cell
Cytoskeleton
78
What links cadherins and integrins to actin filaments or intermediate filaments
Adapter proteins
79
The adapter protein interaction provides mechanical continuity from cell to cell in muscles and epithelia, allowing them to:
Transmit forces
Resist mechanical disruption
80
In certain cell types where mechanic forces are constantly present, what is important?
Mechanical continuity
81
Sixth principle of adhesion: Association of ligands with adhesion receptors can _______ leading to changes in gene expression, cellular differentiation, secretion, motility, receptor activation and cell division
Activate intracellular signal transduction pathways
82
Signaling through adhesion receptors allows cells to respond appropriately to _______ with the surrounding matrix or cells
Physical interactions
83
In the linkage of classical cadherins to actin filaments, how many different sites do the extra cellular domain of the cadherin does calcium bind to?
Four
84
On the cadherin, what part of the domain does calcium bind to?
The extracellular domain
85
When more and more calcium binds to the cadherin, and all four sites are bound, what happens to the structure?
It becomes rigid
86
What adaptor and anchor proteins connect the cadherin to the actin filament intracellularly
P120-catenin
Beta-catenin
Other anchor proteins
87
The anchoring and adaptor proteins of the classical cadherin associate what part of the cadherin to the actin filaments?
Cytoplasmic tail
88
Cells attach to the underlying ECM through two types of junctions that are:
Integrin-dependent
89
What are the two types of integrin-dependent junctions that attach the cell to the underlying extracellular matrix?
1. Focal adhesions
2. Hemidesmosomes
90
Which type of integrin-dependent junctions attaches the actin cytoskeleton to fibers of fibronectin
Focal adhesions
91
Which type of integrin-dependent junction connects intermediate filaments to the basal laminae
Hemidesmosomes
92
Integrin-containing cell matrix junctions are found in what types of cells- give examples
Highly motile, weakly adherent cells (keratinocytes)
Strongly adherent, immobile cells (epithelia)
93
In focal adhesions, you get an adhesion plaque with integrins associated with the ECM, and when changes of movement/stretching occur, that results in:
Force transmission through the integrins and into the actin filaments
94
In focal adhesions, when you get force transmission through integrin into the actin filaments this ultimately leads to tugging of:
Proteins in the nucleus
95
What two integrin linkage ancillary proteins are important intracellularly
Talin and vinculin
96
Extracellularly in an integrin linkage, active integrin binds in what type of mechanism
Clamping mechanism
97
Extracellularly in integrin linkages, active integrin binding in a claminping mechanisms between:
Alpha and beta subunits to the extracellular matrix protein
98
Where is the hemidesmosome mainly found
Basal surface of epithelial cells
99
What firmly anchors epithelial cells to the underlying basal lamina
Hemidesmosome
100
What does the cytosolic side of a hemidesmosome consist of?
A plaque composed of adaptor proteins
101
On the cytosolic side of the hemidesmosome the adaptor proteins composing the plaque are attached to:
The ends of keratin filaments
102
What form of integrin is localized to hemidesmosomes
Alpha-6-beta-4
103
What does the integrin alpha-6-beta-4 bind to within the plaques
Plectin (an adaptor protein)
104
What does integrin alpha-6-beta-4 bind to in the ECM
Laminin
105
How do hemidesmosomes increase the overall rigidity of epithelial tissues
By interconnecting the intermediate filaments of the cytoskeleton with fibers of basal lamina
106
It is important to know that hemidesmosomes connect:
The intermediate filaments of the cytoskeleton to the basal lamina
107
What type of filaments do hemidesmosomes attach to on the inside of the cell?
Keratin
108
What do hemidesmosomes attach to on the extracellular matrix side?
Collagen and laminin
109
An important group of anchoring proteins involved in hemidesmosomes
Plectin and dystonin
110
Plectin and dystonin help the hemidesmosomes to
Anchor to the keratin filaments inside the cell
111
What clinical relevance do adhesion proteins play a role in
Platelet function, development, and health/disease
112
What is the first thing that happens after we have an injury to a blood vessel
Spasm that constricts blood vessel
113
What is the second step that occurs after an injury to a blood vessel (after the spasm)
Platelet aggregation to site of injury
114
Platelet aggregation to the site of injury is trying to accomplish:
Platelet plug
115
When we have an exposure of the underlying sub-endothelium what certain molecules are being newly exposed that would have previously been covered up by endothelial cells
Collagen and Von Willebrand factor
116
Blood clotting factor that binds to a specific adhesion molecule called GP1B
Von Willebrand factor
117
The GP1B that Von Willebrand factor binds to is located on:
Platelets
118
When an interaction occurs (either Von Willebrand to GP1B or binding to the collagen matrix) what gets activated?
Platelets
119
In platelet adhesion, once the platelets get activated what do they produce or release
ADP
120
The production or release of ADP from platelets causes a confirmational change in what molecule
GPIIb-IIIa
121
In platelet adhesion process, once GPIIb-IIIa undergoes a conformational change this complex will then bind
Fibrinogen
122
Where is the fibrinogen that the GPIIb-IIIa complex binds during platelet adhesion
In circulation
123
After the GPIIb-IIIa complex binds fibrinogen, the fibrinogen will:
Links multiple platelets together
124
When GPIIb-IIIa binds fibrinogen we ultimately get:
A cross-linking of platelets, causing them to aggregate
125
Aggregation of platelets creates a:
Plug that will prevent blood flow
126
The platelet plug is anchored to the site of the injury through:
Linkage of GP1B to the Von Willebrand factor
127
If you have a deficiency in GP1B, this is known as:
Von Willebrands disease
128
If you have a deficiency in the GPIIb-IIIa this is known as
Glanzmann Thrombasthenia
129
Normally platelets are free flowing and do not have access to:
Collagen and Von Willebrand (bc they’re covered up)
130
What layer of tissue is exposed when damage to the blood vessel occurs
Basal lamina
131
Platelet activation:
1. Damage to blood vessel exposes _______
2. Initial binding of _____
3. Platelets become _______
4. Activated platelets secrete _____
5. Activated platelets _____ over defect
Basal lamina
Platelets
Activated
ADP
Aggregate
132
What is the first independent stimuli that activates platelets
1. Integrin alpha-2-beta-1 binds collagen in basal lamina
133
What is the second independent stimuli that activates platelets
2. Thrombin activates 7-helix receptors
134
What is the third independent stimuli that activates platelets
3. ADP activates 7-helix receptors
135
Platelets aggregate when:
Fibrinogen cross-links
136
It is important that platelet activation only occurs _____ to prevent ____
Locally; systemic clotting
137
E-cadherin
Epithelial cadherin
138
What is two other names for E-cadherin
Uvomorulin and L-CAM
139
E-cadherin is expressed on all _____ even at the one-cell stage
Mammalian embryonic cells
140
Later on in embryogenesis E-cadherin goes fron being expressed in all embryonic cells to being:
Restricted to epithelial tissues of embryos and adults
141
P-cadherin
Placental cadherin
142
P-cadherin appears to be expressed primarily on the
Trophoblast cells
143
Placental cells of the mammalian embryo that contact the uterine wall
Trophoblast
144
It thought that P-cadherin facilitates the connection of the _____ to ____
Embryo; uterus
145
N-cadherin
Neural cadherin
146
N-cadherin is first seen on _____ cells in the gastrulating embryo as they lose their E-cadherin expression
Mesodermal
147
N-cadherin is seen highly expressed on the:
Cells of the developing nervous system
148
Cadherins join together by binding to the same type of cadherin on another cell (E-cadherin sticks best to other cells with E-cadherin and will sort out from N-cadherin cells)
What type of pattern is this?
Homophilic binding
149
Cell sorting is driven by
Cadherins
150
When the cells of different tissues in the developing embryo are dissociated, mixed and then allowed to re-aggregate what occurs and what drives this process
Cells assort back into their respective layers/tissues - this is due to cadherin
151
Cadherins can be ______ in their expression
Spatially restricted
152
Cell concentration of cadherins, and how they are spatially restricted in the neural tube leads down the differentiation pathway to the formation of:
More and more complex tissues
153
What are the functional roles of the basal lamina
1. Molecular filter
2. Cell barrier
3. Molecular scaffolding to aid in regeneration after injury
154
Retaining proteins in the blood, while filtering toxic substance into the urine pertains to what role of the basal lamina
Molecular filter
155
In tooth formation, the ameloblasts and odontoblasts are separated by a basement membrane- what role of the basal lamina is this describing?
Cell barrier
156
Protein involved in many steps of cell migration
Vinculin
157
During traction force generation _____ links ______ to the actin cytoskeleton and bears the forces exerted during motility
Vinculin; integrins
158
Vinculin can interact with _____ to induce a conformation change that reduces vinculins interaction with actin, thereby promoting the disassembly of focal adhesions
PIP2
159
Certain types of cells move and do so because of their ability to vary the ____ of interaction with the ECM at one part of the cell relative to another part of the cell
Avidity
160
Vinculin plays a role in what type of cell migration
Polarized
161
What are the three steps of transendothelial migration in the nervous system
1. Capture and rolling
2. Activation and adhesion
3. Migration
162
Transendothelial migration is really important in:
Vasculature
163
Loose association of cells and tight association and activation of certain receptors is characteristic of what process
Transendothelial migration
164
Defects in leukocyte function are often associated with:
Mutation in adhesion molecules
165
Leukocytes adhesion deficiency has a severe tooth phenotype that is associated with:
Extreme caries and gingivitis
166
In a normal individual what are transmigrating through the vasculature and into the tissue
Neutrophils
167
Normal individuals with transmigration-competent neutrophils have the presence of neutrophils that restrains the expression of _____ to normal levels
IL-23
168
What type of neutrophils do individuals with LAD contain
Transmigration-incompetent neutrophils
169
LAD
Leukocyte adhesion deficiency
170
In LAD individuals the absence of neutrophil regulation unleashes the overexpression of ______ and downstream cytokines _____ and _____
IL-23; IL-17 & G-CSF
171
It is important that our neutrophils prevent the release of IL-23 because IL-23 leads to the activation of another cell that secretes
IL-17
172
Targets tissue fibroblasts to release G-CSF
IL-17
173
What does G-CSF in normal levels do
Regulated granulopoiesis
174
An increased level of IL-17 leads to inflammatory bone loss and dysbiosis ultimately leads to
LAD-associated periodontitis
175
In addition to causing LAD-associated periodontitis, an increase in IL-17 can cause increase in GCSF, which causes
Excessive granulopoiesis
176
T-Cells use cell adhesion receptors in the process of:
Antigen presentation
177
In order for ________to occur a cassette (many) cell adhesion molecules must be expressed and have to bind to their receptors on the other opposing cell
Clonal expansion of T-cell
178
Cellular adhesion molecules play a role in the regulation of T-cell:
Response to antigen
179
Cell adhesion receptors participate in process of sensation and response to
Mechanical forces
180
What activates signaling pathways at adhesion sites?
Mechanical tension
181
Cause the dissociation or de-adhesion of cells to the ECM or between cells
Disintegrins
182
What sequence do many disintegrins contain
RGD
183
The RGD sequence contained by many disintegrins is also present in many
ECM proteins
184
By binding to integrins on the surface of cells, disintegrins:
Competitively inhibit binding of cells to matrix components
185
Many disintegrins are present in snake venom, which prevent ______ and are partially responsible for the anticoagulant property of venoms
Platelets from aggregating
186
What are the two classes of de-adhesion factors?
1. Disintegrins with the RDG sequence
2. De-adhesion factors that contain the proteases ADAMs and MMPs
187
Membrane bound proteases that catalyze shedding of transmembrane proteins
ADAMs (ADAMS-TS)
188
A soluble enzyme that cleaves non-fibrillation ECM proteins
ADAM-TS
189
Because ADAM-TS enzymes degrades the ECM matrix components it functions to
Facilitate cell migration
190
Bu binding of the integrins through their RGD sequence, the disintegrins:
Competitively inhibit binding of cells to matrix
191
MMPs
Matrix-specific metalloproteases
192
Responsible for proteolytic degradation of transmembrane adhesion molecules
ADAMs or MMPs
193
Any time there is some kind of force whether its stress of tension applied to ECM that will be transferred through:
The integrins to the actin filaments
194
An adaptor proteins that when it changes its conformation it changes how the fibers inside the cell behave (like actin) and creates a mechanism for cells to move
Vinculin
195
Subcellular structures through which mechanical force and regulatory signals are transmitted between the ECM and cell interior
Focal adhesion
196
Very small stud-like structures found in keratinocytes of the epidermis of skin that attach to the extracellular matriz
Hemidesmosome
197
Transmembrane receptors composed of heterodimer is subunits which were products of two separate genes
Integrin receptors
198
Mediates both cell-cell and cell-ECM adhesion
Integrin family of transmembrane adhesion receptors
199
To increase the affinity of integrin receptors for their extracellular ligands
Integrin activation
200
Integrin activation is controlled by intracellular signals that through their action on ______ induce confirmational changes in the integrin extracellular domains that result in increase affinity for there ligand
Integrin cytoplasmic domain
201
Cell membrane receptor by which cells specifically recognize eachother and adhere to eachother
Cell-cell adhesion receptor
202
Cell membrane receptor by which cells specifically recognize cell matrix proteins and adhere to them
Cell-matrix adhesion receptor
203
ICAM-1 is an example of what type of receptor?
Fibronectin is an example of what type of receptor?
Cell to cell
Cell to matrix
204
What are the two subunits that the leukocyte adhesion receptor is composed of
CD18 and CD11a
205
What ligand is associated with leukocytes function associated antigen-1
ICAM
206
LFA-1 typically exists in:
Inactive state
207
When LFA-1 is in its typical inactive state, it has ____ affinity for ICAM
Low
208
When LFA-1 is in its activated states it has _____ affinity for ICAM
Enhanced
209
What stimulates the activation of LFA-1
Chemokines
210
What is an ICAM
Intercellular adhesion molecule
211
Important in inflammation, immune response, and intracellular signaling
ICAM
212
A type of adhesion molecule important in formation of adheren junctions to bind cells to eachother (calcium dependent)
Cadherins
213
Small proteins from viper venoms which function as potent inhibitors of both platelet aggregation and integrin-dependent adhesion
Disintegrins
