| Project/Area Number |
16500243
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Neurochemistry/Neuropharmacology
|
|---|
| Research Institution | HIROSHIMA UNIVERSITY |
|---|
Principal Investigator |
SAKAI Norio Hiroshima University, Graduate School of Biomedical Sciences, Professor, 大学院・医歯薬学総合研究科, 教授 (70263407)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
MATSUBAYASHI Hiroaki Hiroshima Univ., Gradate School of Biomedical Sciences, Associate Professor, 大学院・医歯薬学総合研究科, 助教授 (60165850)
AMANO Taku Hiroshima Univ., Graduate School of Biomedical Sciences, Assistant Professor, 大学院・医歯薬学総合研究科, 講師 (10294547)
TAKAHIRO Seki Hiroshima Univ., Graduate school of Biomedical Sciences, Research Associate, 大学院・医歯薬学総合研究科, 助手 (50335650)
|
|---|
| Project Period (FY) |
2004 – 2005
|
| Project Status |
Completed (Fiscal Year 2005)
|
| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2004: ¥2,200,000 (Direct Cost: ¥2,200,000)
|
|---|
| Keywords | protein phosphorylation / protein kinase C / Purkinje cell / transgenic mice / Propagation on neuronal excitation |
|---|
| Research Abstract |
1)We developed brain region specific and inducible transgenic mice expressing gammaPKC-GFP using tet-regulated system. In these mice, gammaPKC-GFP was abundantly expressed in Purkinje cells. We prepared the cerebellar slices from these mice and attempted to observe gammaPKC-GFP translocation in living Purkinje cells. Trans-synaptic stimulation of parallel fiber triggered gammaPKC-GFP translocation along the dendritic shafts. This translocation propagated from peripheral to soma of the cells, indicating that neural activity can control gammaPKC translocation. This phenomenon provides the novel insight for developing the methods to monitor the neural activity in a protein level.
2)Recently it was reported that the hereditary spinocerebellar ataxia type 14 (SCA14) is caused by missense mutations of gammaPKC. To elucidate the molecular mechanism underlying the SCA14 pathogenesis, we introduced SCA14 mutations into human gammaPKC cDNA, fused it with GFP cDNA and expressed mutant gammaPKC-GFP in CHO cells. The aggregation of mutant gammaPKC was obviously seen in the expressing cells. Moreover, gammaPKC-GFP was frequently aggregated during the process of its receptor-mediated translocation. These results suggest that the aggregate formation of mutant gammaPKC is involved in the SCA14 pathogenesis.
3)We performed PCR-based screening of genomic DNA prepared from undefined Japanese SCA patients. We found new Japanese SCA14 family and proved that SCA14 is very rare in Japanese SCA population.
|
