| Abstract No.: | A-B1070 |
| Country: | Canada |
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| Title: | ROLE OF SYNAPTOTAGMIN-DYNAMIN INTERACTION IN MAMMALIAN SYNAPTIC VESICLE ENDOCYTOSIS |
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| Authors/Affiliations: | 1 Robyn McAdam*; 1 Fiona Young; 1 Vanessa Bedford; 1 Wayne Sossin;
1 McGill University, Montreal, QC, Canada
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| Content: | Synaptotagmin I (Syt I) is a membrane protein located on synaptic vesicles that is important for calcium-dependent neurotransmitter release and for vesicle endocytosis. Syt I contains several domains, including a highly conserved, but poorly studied, juxtamembrane domain. Recent research suggests that splice variants of this domain may have an undetermined role in the regulation of synaptic vesicle endocytosis. Synaptic endocytosis may occur through multiple mechanisms, including the classic clathrin-mediated endocytosis. An alternative mechanism called kiss-and-run is thought to be clathrin-independent. We found that Dynamin, a GTPase involved in clathrin-mediated endocytosis, interacts with Syt I through the juxtamembrane domain. Glutathione-S-transferase fusion protein pull-down assays using rat brain extract suggest that Syt I, splice variants of Syt I, and isoform Syt II have differing binding affinities to Dynamin. A specific variant of Syt I that contains the insertion of the three amino acids ALK (Syt IALK) appears to bind more strongly to Dynamin than does Syt I, whereas Syt II does not appear to bind Dynamin. Surprisingly, the nine amino acid insert that distinguishes Syt I from Syt II is not required for binding. Syt I is phosphorylated by PKC at a site in the juxtamembrane domain. Converting the threonine at this site to a glutamic acid to mimic PKC phosphorylation strongly decreases Dynamin binding. This research will determine if the Syt-Dynamin interaction is important for the regulation of synaptic vesicle endocytosis. |
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