2000 Fiscal Year Final Research Report Summary
Mode of actions and functions of the Rab3A and SNARE systems in neurotransmitter release
| Project/Area Number |
11670118
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
General medical chemistry
|
|---|
| Research Institution | DOKKYO UNIVERSITY SCHOOL OF MEDICINE |
|---|
Principal Investigator |
SHIRATAKI Hiromichi The Division of Molecular and Cell Biology, Institute for Medical Science, DOKKYO UNIVERSITY SCHOOL OF MEDICINE, Professor, 医学部, 教授 (90249962)
|
|---|
| Project Period (FY) |
1999 – 2000
|
| Keywords | Neurotransmitter / Rab3A system / SNARE system / Small GTPase |
|---|
| Research Abstract |
It has been revealed that the Rab3A, a small GTPase, and SNARE systems are involved in neurotransmitter release. The Rab3A system consists of its target protein, which interacts with the GTP-bound form of Rab3A but not with the GDP-bound form of Rab3A, and its several regulatory proteins. We have identified Rabphilin-3 as a target protein for Rab3A and revealed the possibility that Rabphilin-3 functions as a Ca^<2+>-sensor in the presynapse. On the other hand, available evidence suggests that the SNARE system functions at the downstream of the Rab3A system and is implicated in neurotransmitter release. We have identified Tomosyn as a regulatory protein of the SNARE system. It is possible that Tomosyn is a central player which links between the Rab3A and SNARE systems. However, the mechanism by which the Rab3A system regulates the SNARE system in neurotransmitter release remains to be clarified. Therefore, in this study we attempted to clarify the mechanism. We revealed that there were at least three isoforms of Tomosyn, b-, m-, and s-Tomosyns and that all of the tomosyn isoforms interacted through their C-terminal VAMP-like regions with syntaxin-1 but not with other syntaxin isoforms such as syntaxin-2, -3, and -4. Moreover, we identified a novel syntaxin-1-binding protein. On the basis of its biochemical properties, it was possible that the syntaxin-1-binding protein was a cytoskeleton-related protein. One mole of the syntaxin-1-binding protein bound to about 0.8 mole of syntaxin-1 and the dose giving the half maximal binding of syntaxin-1 to the syntaxin-1-binding protein was about 90 nM.The interaction of the syntaxin-1-binding protein with syntaxin-1 was inhibited by Munc18 in a dose-dependent manner. In future we attempt to purify the syntaxin-1-binding protein, determine its primary structure, and reveal its function in neurotransmitter release.
|
-
-
-
-
-
-
-
-
[Publications] Shirataki, H., Sasaki, T., and Takai, Y.: "Rabphilin-3 : a target molecule for Rab3 small G proteins."Methods in Enzymolog, (Balch, W.E., Der, C.J., and Hall, A., eds.). 329. 75-82 (2000)
Description
「研究成果報告書概要(欧文)」より
