2018 Fiscal Year Final Research Report
Molecular anatomy of photoreceptor ribbon synapses with special attention to the ADP ribosylation factor 6 (Arf6) pathway
| Project/Area Number |
15H04672
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
General anatomy (including histology/embryology)
|
|---|
| Research Institution | Kitasato University |
|---|
Principal Investigator |
|
|---|
| Research Collaborator |
FUKAYA Masahiro
HARA Yoshinobu
|
|---|
| Project Period (FY) |
2015-04-01 – 2019-03-31
|
| Keywords | リボンシナプス / 視覚 / 筋ジストロフィー / 小胞輸送 |
|---|
| Outline of Final Research Achievements |
The aim of this study is to provide the functional importance of the ADP ribosylation factor 6 (Arf6) pathway in the photoreceptor ribbon synapse. By immunofluorescence and immunoelectron microscopy using a novel anti-BRAG2a antibody, we found that BRAG2a, a guanine nucleotide exchange factor specific for Arf6, colocalized to the plasma membrane of lateral walls and processes of photoreceptor terminals within the synaptic cavity with dystroglycan and dystrophin. Pull-down and immunoprecipitation assays using the retinal lysate demonstrated the complex formation of BRAG2a with the dystrophin and beta-dystroglycan. The present study provides evidence for BRAG2a as a novel component of the photoreceptor dystrophin-associated glycoprotein complex (DGC), suggesting the possible functional involvement of the BRAG2a-Arf6 pathway downstream of the DGC in synaptic organization of photoreceptors.
|
| Free Research Field |
神経解剖学
|
| Academic Significance and Societal Importance of the Research Achievements |
ヒトの外界からの情報の大半は視覚に依存しており、視覚障害が生活の質(QOL)に与える影響は著しく大きい。網膜の視細胞は、明暗・色調を鋭敏に感知して神経伝達物質を持続的に放出する特殊なシナプス「リボンシナプス」を持つ。しかしながら、リボンシナプスの生理学的特性を支える分子制御機序は未だ不明である。本研究は、低分子量G蛋白質Arf6経路の網膜リボンシナプスでの機能を明らかにするために実施した.
その結果、視細胞リボンシナプスにおいてArf6活性化制御因子BRAG2aがジストロフィン複合体を形成することを見出し、リボンシナプスの形成・維持に関わる新たな制御経路である可能性を示した。
|
