Cellular Adhesion- Exam III Flashcards
What are tight junctions categorized as?
Occluding junction
What seals gaps between epithelial cells and the restricts the flow of substances between cells and forces the substance to go through the cell
Tight jxn
What type of junctions are cell-cell anchoring junctions?
Adherens & Desmosomes
What type of junction connects the actin filament bundles in one cell to that in the next cell?
Adherens junctions
What type of junction connects the intermediate filaments in one cell to those in the next cell
Desmosomes
What type of junction is a gap junction categorized as?
Channel-forming junction
What type of junction allows the passage of small water-soluble molecules form cell to cell?
Gap junction
What are our types of cell-matrix anchoring junctions?
- Actin- linked cell matrix adhesion anchors
- Hemidesmosomes
What type of junction anchors actin filaments in cell to the ECM?
Actin-linked cell-matrix adhesion anchor-
What type of junction anchors intermediate filaments in a cell to the ECM?
Hemidesmosomes
What are the adherens junctions transmembrane adhesion protein?
Cadherins
What are the desmosomes transmembrane adhesion protein?
Cadherin
Actin-linked cell matrix adhesion anchors use what type of transmembrane protein?
Integrin
Hemidesmosomes use what type of transmembrane adhesion protein?
Integrin and collagen
We have junctions that connect _____ to _____ and then junction s that connect _____ to _____.
Cells to cells
Cells to ECM basement membrane (Basement lamina)
What cellular junctions involve the ECM?
- Actin-linked cell matrix adhesion anchors
- Hemidesmosomes
What cell junctions involve cell-cell connections?
- Tight junctions
- Adherens
- Desmosomes
- Gap junctions
How many principles are there for cell adhesion?
6
Principle one: How doe cells define their capacity for adhesion?
By selective expressing certain plasma membrane receptors
When cells define their capacity for adhesion, they selectively express certain plasma membrane receptors, what are these receptors?
Cell adhesion molecules (CAMs)
CAMs generally have:
Limited ligand binding activity
Generally cells expressing the proper mix of receptors is part of a genetic program for the:
Differentiation of the cell
Second principle: many adhesion proteins bind ______, and many ligands bind _______.
Bind one main ligand; bind a single type of receptor
In accordance to the one-to-one pairing rule for adhesion proteins binding one main ligand or ligands binding a single receptor, there are many:
Exceptions to this rule
What is an example of an exception to the one to one binding rule to the second principle of adhesion
Integrin family of receptors
The integrin family of receptors generally bind:
More than one ligand
Some ligands such as fibronectin, bind:
More than one integrin
What is the family of cellular adhesion molecules that prefer to bind to themselves (they promote the adhesion of like cells)
Cadherins
When a cell adhesion molecule binds itself promoting the adhesion of like cells is an example of what type of interaction?
Hemophiliac interaction
Association of like receptors on two cells
Homophilic interaction
Cadherins require
calcium
What do selectins bind?
Anionic polysaccharides
Selectins generally bring:
Two different cell types together
What would bind an anionic polysaccharide like those on mucins?
Selectins
What do most Ig-CAMS bind?
Other cell surface adhesion proteins
Association of unlike receptors on two cells
Heterophilic interaction
Ig-CAMS display what type of binding interactions?
Heterophilic interactions
Cadherins are associated with ______ interactions while Ig-CAMS are associated with _____ interactions
Homophilic; heterophilic
What type of cellular adhesion molecules bind a variety of ligands and ECM molecules?
Intergrins
Examples of an ECM molecules that integrin may bind:
Fibronectin and Laminin
Example of a soluble protein that Integrin may bind:
Fibrinogen
Soluble protein that circulates in the blood and functions in the clotting pathway
Fibrinogen
What is the transmembrane protein associated with adherens junctions?
Classical cadherin
What extracellular ligand does adherens junctions bind to?
Cadherin in the neighboring cell
What intercellular cytoskeletal attachment is involved with adherens junctions?
Actin filaments
Adherens junctions and desmosomes are both:
Cell-cell junctions
What transmembrane adhesion proteins are associated with desmosomes?
Cadherin (Desmoglein & Desmocollin)
What extracellular ligand is associated with desmosomes?
Desmoglein an desmocollin in neighboring cell
What intracellular cytoskeletal attachment is associated with desmosomes?
Intermediate filaments
Actin-lined cell- matrix adhesion molecules and hemidesmosomes are both:
Cell-matrix junctions
What is the transmembrane adhesion protein is associated with actin linked cell matrix adhesion junctions?
Integrin
What extracellular ligand is associated with actin-linked cell matrix adhesion?
ECM proteins
What intracellular cytoskeletal attachment is associated with actin-linked cell-matrix adhesion junctions?
Actin filaments
What transmembrane adhesion protein is associated with hemidesmosomes?
Integrin and collagen
What extracellular ligand is associated with hemidesmosomes?
Extracellular matrix protein
What intracellular cytoskeletal attachment is associated with hemidesmosomes?
Intermediate filaments
Generally speaking, anchoring proteins do not directly bind to the intercellular filaments but do so through:
Recruitment of anchoring filament
Third principle: How do cells modulate there adhesion?
- Controlling the surface density
- Controlling state of aggregation
- Controlling state of activation
(Of adhesion receptor)
____ reflects not only the level of synthesis but also the portioning of adhesion molecules between teh plasma membrane and intracellular storage compartments
Surface adhesion
An example of cells modulating surface density, state of aggregation, and state of activation of their adhesion receptors is:
Endothelial cells expressing p-selectin
What do cadherins control?
The selective assortment of cells
Cells can sort themselves out according to ___ and ___ of the cadherins they express
Type & Level
Cells can also separate out based on the ____ of the cadherins they express
Density
What are calcium dependent adhesion molecules?
Cadherins
What are cadherins critical for?
Establishing and maintaining intercellular connections
Cadherins appear to be crucial to the:
Spatial segregation of cell types
How are cadherins anchored into the cell?
Catenins
What is the anchoring complex of proteins for cadherins?
Catenins
The cadherin-catenin complex forms the ____ junctions that connect epithelial cells together
Classic adherens junctions
What do catenins bind to in the cytoskeleton of the cell?
Actin
What is the cadherin bridge dependent on?
Calcium
4th principal of adhesion: The rates of ____ and ___ are important determinants of cellular adhesion
Ligand binding and dissociation
When a cell surface adhesion protein binds their ligands weakly, this allows for:
Rapidly reversible interactions
When multiple weak interactions cluster together to stabilizes the adherens and desomsomes junctions- the combined strength of these bonds is said to increase the:
Avidity of the interaction
Strength of interaction:
Avidity
Fifth principle: What do many adhesion receptors interact with inside the cell?
Cytoskeleton
What links cadherins and integrins to actin filaments or intermediate filaments
Adaptor proteins
The adaptor protein interaction provides mechanical continuity from cell to cell in muscles and epithelial, allowing them to do what? (2)
1- transmit forces
2- resist mechanical disruption
In certain cell types where mechanical forces are constantly present, what is important?
Mechanical continuity
Sixth principle: Association of ligands with adhesion receptors can ____, leading to changes in gene expression, cellular differentiation, secretion, motility, receptor activation and cell division
Activate intracellular signaling transduction pathways
Signaling through adhesion receptors allows cells to respond appropriately to _____ with the surrounding matrix or cells
Physical interactions
In the linkage of classical cadherins to actin filaments, how many different sites of the extracellular domain of the cadherin does calcium bind to?
4
On the cadherin, what part does calcium bind to?
Extracellular domain
As more and more calcium binds to the cadherin and all 4 four sites are bound, what happens to the structure?
It becomes rigid
What adaptor and anchor proteins connect the cadherin to the actin filament intracellularly?
P120 catenin, Beta-catenin, and other anchor proteins
The anchoring and adaptor proteins of the classical cadherin associate what part of the cadherin to the actin filaments?
Cytoplasmic tail
Cells attach to the undelrying ECM thorugh two types junctions that are:
Integrin-dependent jxns
What are the two types of integrin-dependent junctions that attach the cell to the underlying ECM?
Focal adhesions and hemidesmosomes
One of the types of integrin dependent junctions attaches the actin cytoskeleton to fibers of fibronectin.. which one is this?
Focal adhesion
One type of integrin-dependent junction connects intermediate filaments to the basal laminae:
Hemidesmosomes
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)
In focal adhesions, you get an adhesion plaque where you have the integrins associated with the ECM, and when changes in movement/ stretching occur, that results in:
Force transmission through the integrins and into actin filaments
In focal adhesions, when you get force transmission through integrin and into the actin filaments, this ultimately leads to tugging of:
Proteins in the nucleus
What two ancillary proteins of integrin linages are important intracellularly
Talin and vinculin
Extracellularly in an integrin linkage, you cave active integrin binding in what type of mechanism?
Clamping
Extracellularly in integrin linkages, you have active integrin binding in a clamping mechanism between:
Alpha and beta subunits to ECM protein
Where is the hemidesmosome mainly found?
Basal surface of epithelial cells
What firmly anchors epithelial cells to the underlying basal lamina?
Hemidesmosomes
What does the cytosolic side of a hemidesmosome consist of?
A plaque composed of adaptor proteins
On the cytosolic side of the hemidesmosome, the adaptor proteins composing the plaque are attached to:
Ends of keratin filaments
What form of integrin is localized to hemidesmosomes?
Alpha6 beta4
What does the integrin alpha6beta4 bind to within the plaques?
Plectin (adaptor protein)
What does integrin alpha6beta4 bind to in the ECM?
Laminin
How do hemidesmosomes increase the overall rigidity of epithelial tissues?
By interconnecting the intermediate filaments of the cytoskeleton with fibers of basal lamina
What type of filaments do hemidesmosomes attach to on th inside of the cell?
Keratin
What do hemidesmosomes attach to on the ECM side of the cell?
Collagen and laminin
An important group of anchoring proteins involved with hemidesmosomes are:
Plectin and dystonin
Plectin and dystonin help the hemidesmosomes to:
Anchor to the keratin filaments inside the cell
What clinical relevance do adhesion proteins play a role in?
Platelet function, development, and health/disease
What is one of the first things that happens after injury to a blood vessel?
Spasm that constricts blood vessel
After injury to blood vessel, after the spasm what occurs?
Platelet aggregation to site injury
Platelet aggregation to the site of injury is trying to accomplish:
Platelet plug
When we have an exposure of the underlying subendotheliun, what certain molecules get exposed that would have previously been covered up by endothelial cells?
Collagen & Von Willebrand factor
Clotting factor that binds to a specific adhesion molecule (GP1b)
Von Willebrand factor
The GP1b that the von willebrand factor binds is present on:
Platelets
When an interaction occurs (either von willebrand to GP1b) or (binding to the collagen matrix) what gets activated?
Platelets
In platelet adhesion once the platelets get activated, what do they produce or release?
ADP
The production or release of ADP from platelets causes a conformational change in what molecule?
GP2b-3a
In platelet adhesion, once GP2b-3a undergoes a conformational change, this complex then binds what?
Fibrinogen
Where is the fibrinogen that the GP2b-3a complex binds during int platelet adhesion?
In circulation
After the GP2b-3a complex binds fibrinogen, the fibrinogen then:
Links multiple platelets together
When GP2b-3a binds fibrinogen we ultimately get:
A cross-linking of platelets causing them to aggregate
The aggregation of platelets creates a:
Plug that will prevent bloodflow
The platelet plug is anchored to the site of the injury through:
Linkage of GP1b to the von willebrand factor
If you have a deficiency in GP1b, this is known as:
Von Willebrand disease
If you have a deficiency in GP2b-3a complex, this is known as:
Glandzmann thrombasthenia
Normally platelets are free flowing and don’t have access to:
Collagen & Von Willebrand factor (because they are covered up)
What layer of tissue is exposed when there is damage to a blood vessel?
Basal lamina
Platelet activation:
1. Damage to blood vessel exposing ______.
2. Initial binding of ____.
3. Platelets become ____.
4. Activated platelets secrete ____.
5. Activated plates _____ over defect
- Basal lamina
- Platelets
- Activated
- ADP
- Aggregate
What is the first independent stimuli that activates platelets?
- Integrin alpha2beta1 binds collagen in basal lamina
What is the 2nd independent stimuli that activates platelets?
Thrombin activates 7-helix receptors
What is the 3rd independent stimuli that activates platelets?
ADP activates 7-helix receptors
When do platelets aggregate?
When fibrinogen cross links
Platelet activation must only occur _____ to prevent _____.
Locally; randomized clots
E cadherin refers to what?
Epithelial cadherin
What is two other names for E-cadherin?
Uvomorulin and L-CAM
E-cadherin is expressed on all ______, even at the 1-cell stage.
Early mammalian embryonic cells
Later on in embryogenesis, E-cadherin goes from being expressed in all embryonic cells to being:
Restricted to epithelial tissues of embryos and adults
P- cadherin:
Placental cadherin
P-cadherin appears to be expressed primarily on the:
Trophoblast cells
What are the placental cells of the mammalian embryo that contact the uterine wall?
Trophoblast cells
It is thought that p-cadherin facilitates the connection of the ____ to the ____.
Embryo to the uterus
N- cadherin:
Neural cadherin
N-cadherin is first seen on _____ cells in the gastrulating embryo as they lose their E-cadherin expression
Mesodermal cells
N-cadherin is highly expressed on the:
Cells of the developing nervous system
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 called?
Homophillic binding
Cell sorting is driven by:
Cadherins
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?
Cell assort back into their respective layers & driven by cadherin
Cadherins can be _____ in their expression
Specially restricted
Cell concentration of cadherins and how they are specially restricted in neural tube tissues leads down the differentiation pathway to the formation of:
More and more complex tissues
What are the functional roles of the basal lamina?
- Molecular filter
- Cell barrier
- Molecular scaffolding to aid in regeneration after injury
Retaining proteins in the blood while filtering toxic substances into the urine pertains to what role of the basal lamina?
Molecular filter
In tooth formation, the ameloblasts and odontoblasts are separated by a basement membrane, what role of the basal lamina is this describing?
Cell barrier
What protein is involved in many steps of cell migration?
Vinculin
During traction force generation, ____ links ____ to the actin cytoskeleton and bears the forces exerted during motility.
Vinculin links integrins
Vinculin can also interact with ___ to induce a conformational change that reduces Vinculin interaction with actin, thereby promoting the disassembly of focal adhesions.
PIP2
Certain types of cells move and do so because of their ability vary the _____ of interaction with the ECM at one part of the cell relative to another part of the cell.
Avidity
Vinculin plays a role in what type of cell migration?
Polarized
What are the 3 steps of transednothelial migration in the nervous system?
- Capture & rolling
- Activation & adhesion
- Migration
Transendothelial migration is really important in:
Vasculature
Loose association of cells and tight association and activation with certain receptors is characteristic of what process?
Transendothelial migration
What is the process by which a leukocyte squeezes the cells in Transendothelial migration in the vasculature
Extravasation
Defects in leukocyte function are often associated with:
Mutations in adhesion molecules
Leukocyte adhesion deficiency has a severe tooth phenotype that is associated with:
Extreme caries and gingivitis
In a normal individual, what are transmigrating through the vasculature into the tissue?
Neutrophils
Normal individuals with transmigration competent neutrophil s have a presence of neutrophils that restrains the expression of _____ to normal levels
IL-23
In individuals with LAD, what type of neutrophils do they have?
Transmigration-incompetent neutrophils
LAD stand for:
Leukocyte adhesion deficiency
In LAD individuals, the absence of neutrophil regulation unleashes the overexpression of ____ and downstream cytokines ___ & ____
IL-23
IL17 & GCSF
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
What targets tissue fibroblasts to release G-CSF?
IL-17
What does G-CSF in normal levels do?
regulates granulopoeisis
Increased IL-17 leads to inflammatory bone loss and dysbiosis ultimately causing:
LAD-associated periodontitis
In addition to causing LAD-associated periodontitis, the increase in IL-17 can cause increase in G-CSF which causes:
Excessive granulopoeisis
T-cells use cell adhesion receptors in process of:
Antigen presentation
In order for ________ to occur, a cassette (many) cell adhesion molecules have to be expressed and have to bind to heir receptors on the other opposing cell
Clonal expansion of T cell
Cellular adhesion molecules play a role in the regulation of T-cell:
Responses to antigen
Cell adhesion receptors participate in process of sensation and response to:
Mechanical forces
What activates signaling pathways at adhesion sites?
Mechanical tension
What causes the dissociation or deadhesion of cells from the ECM or between cells?
Disintegrins
What sequence do many disintegrins contain?
RGD sequence
The RGD sequence in many disintegrins is also present in many
ECM proteins
By binding to integrins on the surface of cells, disintegrins:
Competitively inhibit binding of cells to matrix components
Many disintegrins are present in snake venom which prevents _____ and are partially responsible for the _____ property of venoms
Platelets from aggregating; anticoagulant
What are the two classes of deadhesion factors?
1) Disintegrins with RGD sequence
2) Deadhesion factors that contain proteases ADAMs and MMPs
What are membrane bound proteases that catalyze shedding of transmembrane proteins
ADAMs
What is a solubl enzyme that cleaves non-fibrillation ECM proteins?
ADAM-TS
Because ADAM-TS enzyme degrades the ECM components, it functions to facilitate:
Cell migration
By binding of the integrins through the RGD sequence, the disintegrins:
Competitively inhibits binding of cells to matrix
MMPS:
Matrix specific metalproteases
What is responsible for proteolytic degredation of transmembrane adhesion molecules?
ADAMs or MMPS
Any time there is some kind of force whether its stress or tension applied to ECM, that will be transferred through:
The integrins to the actin filaments
An adaptor protein that when it changes its conformation it changes how the fibers in side the cell behave (like actin) and creates a mechanism for cells to move
Vinculin
Sub cellular structures through which mechanical force and regulator signals are transmitted between teh ECM and cell interior
Focal adhesion
Very small stud like structures found in keratinocytes of the epidermis of skin that attach to the ECM
Hemidesmosomes
Transmembrane receptors composed of heterodimeric subunits which were products of two separate genes.
Integrin receptor
Mediate both cell to cell and cell to ECM adhesion
Integrin receptors
To increase the affinity of the integrin receptors for their extracellular ligands
Integrin activation
Integrin activation is controlled by intracellular signals that through their action on _____ induce conformation changes in the integrin extracellular domains that result in increased affinity for the ligand.
Integrin cytoplasmic domain
Cell membrane receptor by which cells specifically recognize eachother and adhere to eachother
Cell-cell adhesion receptor
Cell membrane receptor by which cells specifically recognize cell matrix proteins and adhere to them
Cell-matrix adhesion receptor
ICAM-1 is an example or _____ receptor; while fibronectin is an example of _____ receptor
Cell to cell
Cell to matrix
What are the two subunits that leukocyte adhesion receptor is composed of:
CD18 and CD11a
What ligand is associated with Leukocyte function associated antigen-1?
ICAM
LFA-1 typically exists in:
Inactive state
When LFA-1 is in its typical inactive state, is has ____ affinity for ICAM
Low affinity
When LFA-1 is in its activated state, if have ____ affinity for ICAM
Enhanced affinity
What stimulates the activation of LFA-1?
Chemokines
What is an ICAM?
Intercellular adhesion molecule
What is importation in inflammation, immune response, and intracellular signaling?
ICAM
A type of adhesion molecule which is important in formation of adheren junctions to bind cells to eachother, (calcium dependent)
Cadherins
Small proteins from viper venoms which function as potent inhibitor sof both platelet aggregation and integrin-dependent adhesion
Disintegrins
