BIOC 212 Lecture Notes - Lecture 15: Protocadherin, Rac1, Cadherin
39 views6 pages
Lecture 15: Integrins (February 10, 2012)
Lecture 14 (continued)
Cadherin diversity in the CNS
Nerve tissue cadherins have distinct yet overlapping expression patterns
o Found in the brain of a mouse are the classical cadherins
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
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
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.
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
• Are important for cell-cell contact
• Regulate intracellular mechanisms
• 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 cell–cell adhesions.
• Before the establishment of E-cadherin-mediated cell–cell
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
• Activated Rac1 then positively regulates E-cadherin-mediated cell–cell 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)
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.