Cellular Adhesion and Migration Flashcards
Classes of cell junctions in animal tissues
- Anchoring junctions
- Occulding (tight) junctions
- Channel-forming junctions (gap junctions)
- Signal-relaying junctions
Anchoring junctions
Assemble and maintain epithelia; Transmit stresses and mechanically attach cells to their neighbors; consists of transmembrane adhesion proteins that link to cytoskeleton via intracellular anchor proteins
ex. cell-cell adhesions and cell matrix adhesions
Occulding (tight) junctions
seal gaps btwn cells in epithelia; forms selectively permeable barrier
- keeps interstitial fluid inside animal*; always closest to apical domain
- prevent back flow from one side of cell to other
- forms fence btwn membrane domains (cells need to segregate proteins to appropriate domain ie basolateral or apical)
Channel-forming junctions (gap junctions)
link cytoplasm of adjacent cells
Signal-relaying junctions
allows signal relay from cell to cell at PM contact
ex. chemical synapses in nervous system and immunological synapses
junctions that allow cell to form epithelium
anchoring junctions and occluding junctions
cell cell attachments
usually mediated by cadherins
cell matrix attachments
usually mediated by integrins
Anchoring junction components
Transmembrane adhesion proteins (attach to each other btwn PMs) and intracellular adaptor proteins (attach transmembrane adhesion proteins to cytoskeletal filaments)
Catenins
Adaptor proteins that link cell adhesion receptors to cytoskeletal elements; cadherins anchor to cytoskeleton via catenins which assemble on cadherin tail
Actin filament attachment sites
- adherence junctions (cell-cell junctions)
- Actin-linked cell-matrix adhesions (cell-matrix junctions)
Intermediate filament attachment sites
- Desomsomes (cell-cell junctions)
- Hemidesmosomes (cell-matrix junctions)
Adherens junctions
coordinate actin-based motility of adjacent cells; form continuous adhesion belt around interacting cells in epithelial sheet; contract via myosin motor proteins; confer motile force for folding of epithelia sheets
Cordination of actin based motility of adjacent cells
coordinated by adherens junctions; oriented contraction of bundles of actin filaments running along adhesion belts causes narrowing of cells at apex
Desmosomes
link intermediate filaments from cell to cell main job is to confer mechanical strength
desmosomes and hemidesemosomes
along with intermediate filaments form network of great tensile strength; desmosomes link intermediate filaments from cell to cell hemidesmosomes link intermediate filaments to basal lamina?
Pemphigus
autoimmune disease body attacks desmosomal cadherins cells become “unglued” from each other -> severe blistering
Cadherins
mediate cell cell attachment at anchoring junctions (adherens junctions and desmosomes)
CALCIUM DEPENDENT
Cadherin structure
extracellular domain contains cadherin repeats which are joined by flexible hinge regions
Ca2+ binds at linker region -> prevents flexing
Ca2+ absent from linker region -> hinge region floppy
Cadherin binding
cadherins on opp cells bind end to end; binding = homophilic; multiple parallel low affinity bonds allow for strong interactions and easy assembly; intracellular domains highly variable b/c high variety intracellular ligands
homophilic binding cadherin
molecules of specific subtype in one cell only bind cadherins of same or closely related type
Selective assortment of cells
controlled by cadherins; appearance and disappearance of specific cadherins allows cells to regroup and change their contacts to form new tissue structures
Epithelial-mesenchymal transition
epithelial cells can disassemble from parent epithelium and adopt mesenchymal phenotype and migrate away as individual cells via change in expression of adhesion molecules regulated by transcription factors such as twist, snail, and slug
Important in:
-Development
- wound healing (want cells near wound to move in and loose growth inhibition
- cancer
Origin of neural crest
epithelial-mesenchymal transition -cells from epithelial- neural tube alter their adhesive properties, twist represses transcription of e-cadherin Migrate: -chemotaxis -chemorepulsion -contact guidance Reaggregate
cell-cell adhesions and intracellular signaling
there is cross talk between adhesion machinery and cell signaling pathways
- cells attached to other cells proliferation inhibited (contact inhibition)
- attachments btwn cells broken proliferation stimulated (ex wound healing)
Beta catinin
Dual functions serves as anchoring protein at adherens junctions and nuclear transcription factor
Cell location (nucleus vs adherens junction) dictates its fx
- relocates to nucleus during epithelial-mesenchymal transition (bc freed when transition to mesenchymal cell when loose E cadherin so relocates to nucleus)
- mislocalization -> cancer
Occulding junction structure
serve as fence between apical and basolateral domains of polarized epithelial cell (ensures protein segregate to appropriate domain)
branching networks sealing strands encircle apical ends of cell in sheet
** always closest to apical part of cell**
Each strand composed of long row transmembrane adhesion proteins (Claudine and occluding) embedded in interaction PMs; extracellular domains adhere occluding extracellular space
Claudins
one of two transmembrane adhesion proteins (Claudine and occluding) embedded in PM forming occluding junction; Claudins have characteristic ion-conductive properties so type Claudine determine ion-selectivity; differential expression Claudine changes permeability under diff circumstances
alterations in claudins
leads to alteration in permeability can leads to internal cystitis and diabetic retinopathy
- abnormal Claudin expression may be part of pathologic process of feline idiopathic cystitis
tight vs leaky epithelia
differ in permeability of their tight junctinos
- Bladder transitional epithelium= most impermeable epithelium in animal body
- renal tubules= allow paracellular transport
paracellular transport
transport of solutes between cells
How do tight junctions work
Occludins determine permeability to solute
Claudins assemble sealing strands
Organization of cell junctions in epithelial
relative positions diff kinds of junctions are same in all epithelial
Most apical: Occulding junctions -> adherens junctions -> desmosomes (Most basal)
Scaffold proteins = critical components of junctional complexes
Intacelluar scaffold proteins
position and organize tight junctions into correct relationship with other components of junctional complexes
Scaffold proteins
critical components of junctional complexes
- help to establish apico-basal polarity and play key part in control of cell proliferation
cell migration requires
making and breaking of cellular adhesion
leukocyte migration to site of inflammation
1st forms attachment to vascular endothelium then transverses basement membrane and finally crawls through ECM; weak attachment of leukocyte to endothelial sure mediated by cell-surface carbohydrate biding proteins (selectins); stronger adhesions necessary for extravasation mediated by integrins
ECM degredation
integral component migration; mediated by matrix matalloprotinases and serine proteases
FAK
focal adhesion kinase in command and control of cell motility; form intracellular attachment through integrin
Cell motility
- Actin polymerization at forward end
- Membrane delivered to leading edge
- Focal adhesions form at leading edge (localized integrin-mediated attachments at leading edge) providing traction (attachments form at front of lamella podia)
- Integrins recruit FAK at sites cell substrate adhesion
- Tyrosine phosphorylated by FAK creates docking sites for other signaling proteins
- Contraction at rear of cell
- Attachments at rear of cell disassembled to allow forward movement
bovine leukocyte adhesion deficiency
defect in neutrophil Beta2 integrin chain; neutrophils unable to leave blood stream; autosomal recessive
-> pneumonia, enteritis, stomatitis
