BIOC 212 Lecture Notes - Lecture 28: Intermediate Filament, Cytosol, Rac1

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Cell Junctions & Cell Adhesion VIII
!
Compaction of Early Mouse Embryo
Scanning electron micrograph
Cells of mouse embryo first stick together weakly
o Proper cell adhesion molecules are not expressed at early stage (i.e. 4 day
stage)
o At about 8 cell stage, they begin to express E-cadherin --strong & close
adherence
Cells look much more fused due to tight interactions
Cadherin Diversity in CNS
Other types of cadherins expressed at various locations in mouse brain
o E-cadherin
o R-cadherin
o Cadherin-6
In nerve tissue, have many cadherins with distinct but overlapping expression
patterns
o Role in synapse formation & stabilization
Proto-cadherins: in the brain, like antibodies
o In CNS, come in different clusters
3 clusters in humans
o Organized on DNA (genomic)
15 exons that are variable --can be alternatively spliced out
One exon constitute extracellular portion of protein
Green exons (3) code for constant intracellular part of cadherin
o Differ in N-terminal (variable) region, but are identical at C-terminal (constant)
regions
o Encoded by separate exons
Organized in 3 clusters where each of red exons have promoter that drives
transcription of mRNA
o Transcribed into precursor mRNA including
i.e. from V5 to the end
o Then get alternative splicing where almost all red exons spliced out except
one that is most 5'
i.e. Keep V5 and discard V6-V15
o Mechanism to construct different proto-cadherin in CNS
Contains one variable regions and 3 exons coding for constant region
Diversity generated by combination of differential promoter usage & alternative
RNA splicing
o 15 different proto-cadherins
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Document Summary

Cadherin diversity in cns: other types of cadherins expressed at various locations in mouse brain, e-cadherin, r-cadherin, cadherin-6. In nerve tissue, have many cadherins with distinct but overlapping expression patterns: role in synapse formation & stabilization, proto-cadherins: in the brain, like antibodies. Rna splicing: 15 different proto-cadherins, different to antibody diversification by site-specific recombination, antibody is random, but this is specific to location in brain. Linkage & signaling of classical cadherins: cadherins have adaptor molecules, p120, catenins alpha & beta, on top right, have two cells each with their cadherin. Initially, cells are not bound to each other: rac1 molecule (protein that binds gtp/gdp) Interact with gdp-bound small gtpases, inhibit the exchange of gdp for. Gtp, and sequester the small gtpases into the cytosol. Structure of selectins: family of molecules called selectins, similar structure to cadherins, selectin have lectin binding domain at n-terminal.

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