Cell Adhesion Flashcards
1
Q
Classes of Animal Cell Junctions
A
- Anchoring Junctions
- Occluding Junctions
- Channel Forming Junctions
- Signal Relaying Junctions
2
Q
Cell-Cell Adhesions
A
- Epithelial
- cover surfaces, lines cavities, forms barriers, compartments
- minimal ECM at sides
- many cell:cell adhesions and links to cytoskeleton
3
Q
Adherens
A
- anchoring cell junction
- cell:cell
- cadherin as principal CAM (cell adhesion molecule)
- actin filaments (contractile bundle)
- function: shape and tension
- connections actin filament bundle in one cell with that in the next cell
- subjected to pulling forces generated by actin
4
Q
Desmosomes
A
- anchoring cell junction
- cell:cell
- cadherins
- intermediate filaments
- function: mechanical/tensile strength and signalling
- ‘velcro’ effect
- connects intermediate filaments in one cell to those in the next cell
- linkage to similar bundles in adjacent cells to create network
5
Q
Hemidesmosomes
A
- anchoring cell junction
- cell:matrix
- integrin
- intermediate filaments
- function: strength and signalling
- anchors intermediate filaments to the ECM
- a specific integrin anchors the cells to lamina
6
Q
Tight Junctions
A
- cell:cell
- cadherins, JAM, occludins
- actin filaments
- functions: solute flow and signalling
- seals gaps between epithelial cells
- form seal between cells and fence between membrane domains
- epithelial cells are polarized and serve as selective permeability barriers
- contain strands of homophilic TM proteins
- extracellular domains adhere directly to each other to occlude intracellular space
7
Q
Gap Junctions
A
- cell:cell
- connexins, innexins
- cytoskeletal attachment via adaptors
- function: communication and small molecule transport
- allows passage of small water soluble molecules between cells
- couple cells metabolically and electrically
- electrical coupling allows rapid transmission of action potentials
- coordinates cell activities and smoothes out effects of minor concentration fluctuations
- flip between open and closed states triggered by various stimuli
8
Q
Plasmodesmata
A
- cell:cell
- actin filaments
- function: communication and molecule transport
9
Q
Major Families of cell adhesion molecules and adhesion receptors
A
Homophilic: cadherins and immunoglobin superfamily
Heterophilic: Integrins and selectins
10
Q
Cadherins
A
- anchored to membranes but mostly extracellular
- 5 cadherin domains that bind calcium
- short cytoplasmic domain
- cis: 2 cadherins on same cell associate
- trans: 2 cadherins on opposite cells associate
- strong cell to cell adhesions and links to cytoplasm
- adhesion is Ca2+ dependent (3 ions per molecule)
- calcium ions stops hinge flexing so keeps molecule rigid and elongated and increases binding affinity for opposing cadherin molecule slightly
- homophilic binding domain at N terminal
- low affinity attachments individually but in clusters form stronger attachments
11
Q
Cadherin Function
A
- cadherins bind to cadherins of the same type (180 different types)
- this homophilic binding gives identification ‘code’ that is used for cell specialisation and embryo development
- cadherins drive cell recognition and sorting
- cadherins can disassemble and types can change over time (eg. neural crest cells)
- classical cadherin links to the cytoskeleton via 3 adaptor proteins
- mediate highly selective recognition enabling cells of a similar type to stick together and stay segregated
- experiment = amphibian embryos dissociated into single cells reassemble into their specific structure
12
Q
Shape Regulation and Movement
A
- epithelial to mesenchymal stem cell transition
- major role in cancer invasion and metastasis
- epithelial cells have cell to cell adhesion and low motility
- transition to mesenchymal cells with cell matrix interactions and high cell motility / matrix production
- expression of adhesion molecules causes mesenchymal cells to come back together as an epithelium
- epithelial cells can disassemble and migrate away as separate cells
13
Q
Integrins
A
- adhere cell to the ECM
- transverse the membrane
- a/B subunits
- extracellular domains binds to specific sequences like RGO
- ions affect integrin binding to matrix ligands
- allosteric regulation, so ligand binding leads to a conformational change
- mechanotransduction of signals
- integrins > adaptor protein talin > actin filaments
- B chain exposes high affinity talin binding site for actin filament assembly
- or talin binds to the B chain leading to the extracellular part to be activated
- switch between inactive and active states that expose the high affinity binding sites at both ends
14
Q
Ig Superfamily
A
- immunoglobin domains
- about 100 amino acids folded into disulphide bonded B strands
- often glycosylated
- bind to integrins or IgCAM
- weaker adhesion than adherin
- involved in adhesion between blood cells or between blood cells are endothelial cells of blood vessels
- involved in bone marrow cells and blood cell generation & myelin/glial cells
15
Q
Selections
A
- cell surface lectins (carbohydrate binding proteins)
- weak binding that is important in blood cells
- L selectin = white blood cells
- P selectin = platelets/endothelial cells
- G selectin = activated endothelial cells
- Ca ion dependent
- mediates a variety of transient cell:cell adhesion interactions in blood
- govern trafficking of white blood cells intoinflamed tissue by controlling their binding to endothelial cells lining blood vessels
- lectin domain binds to a specific oligosacchride on another cell
16
Q
Blood Cell Rolling
A
- firmer integrin based adhesion allowing extravasion of white blood cells
- selections collaborate with integrins to strengthen the binding of blood cells to the endothelium (heterophilic binding)
- selectin dependent rolling (weak attachment)
- integrin dependent adhesion and emigration (strong attachment)
17
Q
Transmembrane Adhesion Proteins
A
Span plasma membrane with one end linking the cytoskeleton and the other linked to outer structures
- cadherins = cell:cell attachment
- integrins = cell:matrix attachment
18
Q
Cadherin Cell Sorting in Developement
A
Neural Crest Development:
- neural tube cells lose E cadherin and acquire N cadherins
- when the crest cells migrate away from the neural tube, N cadherins disappear and cadherin 7 is expressed
- when cells form ganglion N cadherin is re-expressed
19
Q
Cadherin:Cytoskeletal Linkages
A
- indirect linkages dependent on adaptor proteins assembled at cytoplasmic tail
- adherens: B and p120 catenin
- desmosomes: plakoglobin proteins
20
Q
Assembly of Adherens Junctions
A
- 2 unattached epithelial cell precursors explore their environment with membrane proteins and local nucleation of actin networks
- cell contact means adherin and catenin clusters take shape and associate with actin
- GTPase Ras is activated and promotes further actin protrusions to expand the contact area
- Ras inactivated and replaced by GTPase Rho which shifts actin remodelling to linear filament bundles + promotes myosin II filament assembly
21
Q
Mechanotransduction
A
- a catenin (associated with B unit) is stretched to an extended conformation upon contractile activity
- unfolding exposes binding site for vinculin that promotes actin recruitment
- pulling on junction makes it stronger and increases contractile force generated
22
Q
Tissue Remodelling
A
- continous adhesion belt forms in epithelial cells
- in each cell you have a contractile bundle of myosin II
and actin adjacent to the adhesion belt and parallel to the membrane - the bundles are linked to membrane and contraction gives motile force for epithelial cell folding
23
Q
Connexins
A
- 4 pass TM proteins
- 6 assemble to form a hemichannel (connexin)
- when connexins of 2 contacting cells align they form an aqeous channel
- gap junctions in different tissues are formed from different connexin combinations and differ in permeability
- connection can be heteromeric
24
Q
Integrin Functions
A
Cells have anchorage dependence on substratum to proliferate and survive and integrins mediate this.
Integrins recruit intracellular signalling proteins at sites of cell:matrix adhesions like focal adhesion kinases (FAKs)
