Junctions Flashcards
Integrins
Transmembrane proteins that tie ECM to cytoskeleton.
-bind ligand w low affinity but present in high numbers on cell surface.
Integrin Structure
- 2 required non-covalent units (a and B)
- a contributes to binding specificity
- B interacts with cytoskeleton
- requires divalent cations (Mg++ or Mn++)
Integrin Function
Binds to ligand, then integrin binds to talin and a-actinin, which initiates complex that link integrin to actin.
- this increases intravellular pH and Ca++ levels, and tyrosine phosphorylation.
- also initiates complex of proteins that regulate and catalyze gene expression, cytoskeleton changes, and adhesion.
- binding anchors cell to matrix at discrete sites called focal adhesions. Stress fibers attach here
Focal adhesions
Discrete site where integrin binding anchors cell to matrix
Stress fibers
Bundles of actin that attach to focal adhesions
Leukocyte adhesion deficiency
Loss of exclusive B2 subunit on white blood cells, no adhesion occurs, patients suffer repeated bacterial infections
Glanzmann’s Disease (thrombasthenia)
B3 missing, receptor for fibrinogen doesn’t form, platelets can’t bind to fibrinogen to initiate blood clotting, excessive bleeding occurs.
-treated with platelet transfusion
Selectins
Cell surface carb binding proteins. On endothelial and WBCs
Weaker, allows stronger binding to occur (ICAMs) by slowing WBCs
E selectins
Secreted by endothelial cells.
- bind oligosaccharides on WBCs
- mediate adhesion between WBCs and endothelial cells
P-selectin
Synthesized by platelets
Bind to oligosaccharides on WBCs
L-selection
Synthesized by WBCs
Bind to endothelial cells
Adherin Junction
Connects Cell to cell via Actin
Caderin-catenin-p120-actin
Desmosomes
Connect cell to cell via intermediate filaments
Desmoglein +desmocollin-plakoglobin+plakophillim-desmoplakin-IFs
Hemidesmosoms
Connect cell to matrix via intermediate filaments
Laminin-a6b4(integrin)-bp230+plectrum-IFs
ICAMs
On endothelial cells, bind integrins on WBC surface strongly, trapping them at inflammation
Immune response
Selectins on endothelial cells bind and slow WBCs at specific receptors so integrins on WBCs cam bind to ICAMs strongly
Cadherins
Requires Ca2+.
Cell adhesion by homophonic binding, all cells have
Cadherin structure
Large extra cellular region.
Cadherin links to p120 and B catenin, which links to A-catenin, which links to actin in cytoskeleton
B-catenin, differentiated cells
No Wnt signal. B catenin forms complex, is phosphorylation and degraded.
No binding to Tcf, no transcription
B-catenin, undifferentiated cells
Wnt signal present.
Wnt binds to complex. B-catenin doesn’t get touched, goes to nucleus and forms complex w Tcf, transcription activated.
APC
If APC protein is defective, B catenin in proliferating cells is not degraded and FAP occurs (colon cancer)
Tight junctions
Barrier. Network goes around entire circumference of cell.
Links cells to actin
Occluding/Claudine/JAM-ZO-actin
Gap junction
Allows electrical and metabolic coupling of cytoplasm between cells of a single type, can share small molecules
Charcot-Marie-Tooth disease
Degeneration of peripheral nerves. Loss of muscle control.
Mutation in connexin 32 gene in Schwann cells that rap around nerves and form myelin