Receptors and signal transduction complexes are assembled in a precise manner at
specific subdomains of the plasma membrane. Recent research has implicated scaffolding
proteins in organizing these receptor and signaling complexes. One well characterized
example is the C. elegans LIN-2/LIN-7 /LIN-1 0 complex. This complex is essential in the
proper localization of LET -23, the EGFR ortholog, to the basolateral membrane surface of
vulval epithelial cells.
The mammalian orthologs of the LIN-2/LIN-7 /LIN-10 complex have been
identified. CASKIVELI!Mintl/Xllalpha function as a tripartite complex in neurons,
presynaptically and postsynaptically. Presynaptically, the multi protein complex aids in
linking cell adhesion to ion influx, synaptic vesicle fusion with the presynaptic membrane.
and subsequent neurotransmitter release. At the post-synaptic membrane, the
CASKIVELI!Mintl/Xllalpha complex is hypothesized to function in the sorting and
proper localization of the NMDA type glutamate receptor, reflecting the function of the C.
elegans orthologs in receptor localization.
We have identified the Drosophila orthologs ofLIN-2/CASK, LIN-7NELI, and
LIN-10/Mintl/Xllalpha, termed CMG, dVELI and dMINT. respectively. These proteins
were found to be highly conserved among species. The Drosophila YELl protein was
initially identified by the McGlade laboratory, University of Toronto, where it was found to
bind phosphorylated Drosophila EGFR (DER). We have mapped the chromosomal
location of dveli, determined RNA transcript distribution and protein localization, and
initiated a P-element mutagenesis screen to generate a dveli mutant. Furthermore, candidate
genes for other proteins known to associate with LIN-7 (PALS) have been identified by
sequence analysis.
dVELI expression begins early in the larval stage. It is concentrated mostly in neuropil areas, sites of synaptic connections. This expression pattern continues into adult
development. Within the larval CNS, dVELI protein is localized to the neuropil areas of the
ventral nerve cord and brain. NMJ staining further localizes dVELI almost exclusively to
the post-synaptic density. This post-synaptic localization resembles that of mammalian
YELls, wherein the complex is thought to aid in glutamate receptor sorting and localization.
The similarity in structure and expression patterns of dVELI to that of its mammalian
orthologs suggests a model in which the Drosophila complex aids in the localization of
receptors to post -synaptic specializations in neurons. / Thesis / Master of Science (MSc)
| Identifer | oai:union.ndltd.org:mcmaster.ca/oai:macsphere.mcmaster.ca:11375/22505 |
| Date | 06 1900 |
| Creators | MacMullin, Allison A. |
| Contributors | Jacobs, J. Roger, Biology |
| Source Sets | McMaster University |
| Language | en_US |
| Detected Language | English |
| Type | Thesis |
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