BIOC 212 Lecture Notes - Lecture 15: Protocadherin, Rac1, Cadherin

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Published on 22 Aug 2012
School
McGill University
Department
Biochemistry
Course
BIOC 212
Lecture 15: Integrins (February 10, 2012)
Lecture 14 (continued)
Cadherins
Cadherin diversity in the CNS
Nerve tissue cadherins have distinct yet overlapping expression patterns
Cadherins
o Found in the brain of a mouse are the classical cadherins
E-cadherin
R-cadherin
Cadherin-6
o Are thought to have a role in synapse formation and stabilization of nerve cells.
Proto-cadherins in the brain
o They are like antibodies
o They can create a variety of cadherins because
They differ in their N-terminal region
Variable region exons
o Encode for the extracellular region of one type of transmembrane
proto-cadherin protein
o Many promoters associated with each variable exon that are used to
generate many transcripts.
They are identical in their C-terminal regions
Constant region exons
o Encoded by separate exons
They are arranged on a proto-cadherin gene cluster
Variability is a result of a combination of differential promoter regions and
alternative RNA splicing
o This is very different in comparison to the antibody diversification, which is done by
site-specific recombination.
Figure B, Slide 16, Lecture 14
o The arrangement of exons that encode the members of one of the three known proto-
cadherin families of non-classical cadherins in humans can be seen in the figure above.
o All of the proto-cadherins encoded by this cluster share the same cytoplasmic tail.
Cytoplasmic tail is is encoded by the three constant-region exons C1, C2, and C3.
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Linkage and signaling of classical cadherins
Most cadherins link the actin cytoskeleton of neighboring cells
Cytoplasmic tail of cadherins
Highly conserved
Interact with actin filaments by intracellular anchor proteins called catenins & another
protein called p120 (120kDA big)
Alpha & beta catenins
Essential interaction to hold cells together
Cadherins
Are important for cell-cell contact
Regulate intracellular mechanisms
Desmosomes
Are formed by non-classical cadherins
Interact with IF, rather than with actin filaments.
Their cytoplasmic domains bind different anchor proteins
Signal transduction
Performed by some cadherins
Example: Vascular endothelial cadherin (VE-cadherin)
Mediates adhesion of EC cells and VEGF binds to its receptor and uses VE-cadherin
as a co-receptor.
Figure on the left, Slide 17, Lecture 14
The linkage of classical cadherins to actin filaments.
The cadherins are coupled indirectly to actin filaments by the
anchor proteins alpha-catenin and beta-catenin.
A third intracellular protein, called p120, also binds to the
cadherin cytoplasmic tail and regulates cadherin function.
Figure on the top right, Slide 17, Lecture 14
Mode of activation of Rac1 by the formation of E-cadherin-
mediated cellcell adhesions.
Before the establishment of E-cadherin-mediated cellcell
adhesions, Rho GDI seizes GDP · Rac1 in the cytosol.
When cadherin-mediated homophilic interactions occur, GDP ·
Rac1 is dissociated from Rho GDI by an unknown mechanism
and is targeted to the plasma membrane.
GDP · Rac1 is converted to GTP · Rac1 through the action of a GEF (e.g., Tiam1) downstream
of PI3k.
Activated Rac1 then positively regulates E-cadherin-mediated cellcell adhesions.
Figure on the bottom right, Slide 17, Lecture 14
Activated Rac-1 protein make more actin filament signalling occurs
Net result is the extension of actin filament (polymerization)
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Document Summary

Nerve tissue cadherins have distinct yet overlapping expression patterns. Cadherins: found in the brain of a mouse are the classical cadherins. Cadherin-6: are thought to have a role in synapse formation and stabilization of nerve cells. Proto-cadherins in the brain: they are like antibodies, they can create a variety of cadherins because. Variable region exons: encode for the extracellular region of one type of transmembrane proto-cadherin protein, many promoters associated with each variable exon that are used to. They are identical in their c-terminal regions generate many transcripts. Constant region exons: encoded by separate exons. They are arranged on a proto-cadherin gene cluster. Variability is a result of a combination of differential promoter regions and alternative rna splicing: this is very different in comparison to the antibody diversification, which is done by site-specific recombination. Cytoplasmic tail is is encoded by the three constant-region exons c1, c2, and c3.

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