Cell Adhesion Flashcards

1
Q

Classes of Animal Cell Junctions

A
  1. Anchoring Junctions
  2. Occluding Junctions
  3. Channel Forming Junctions
  4. Signal Relaying Junctions
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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
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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
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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
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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
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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
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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
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8
Q

Plasmodesmata

A
  • cell:cell
  • actin filaments
  • function: communication and molecule transport
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9
Q

Major Families of cell adhesion molecules and adhesion receptors

A

Homophilic: cadherins and immunoglobin superfamily
Heterophilic: Integrins and selectins

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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
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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
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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
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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
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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
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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
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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

  1. cadherins = cell:cell attachment
  2. integrins = cell:matrix attachment
18
Q

Cadherin Cell Sorting in Developement

A

Neural Crest Development:

  1. neural tube cells lose E cadherin and acquire N cadherins
  2. when the crest cells migrate away from the neural tube, N cadherins disappear and cadherin 7 is expressed
  3. 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
  1. 2 unattached epithelial cell precursors explore their environment with membrane proteins and local nucleation of actin networks
  2. cell contact means adherin and catenin clusters take shape and associate with actin
  3. GTPase Ras is activated and promotes further actin protrusions to expand the contact area
  4. 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)