論文 - 詳細
| RRC ID | 79059 |
|---|---|
| 著者 | Bello OD, Jouannot O, Chaudhuri A, Stroeva E, Coleman J, Volynski KE, Rothman JE, Krishnakumar SS. |
| タイトル | Synaptotagmin oligomerization is essential for calcium control of regulated exocytosis. |
| ジャーナル | Proc Natl Acad Sci U S A |
| Abstract |
Regulated exocytosis, which underlies many intercellular signaling events, is a tightly controlled process often triggered by calcium ion(s) (Ca2+). Despite considerable insight into the central components involved, namely, the core fusion machinery [soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE)] and the principal Ca2+ sensor [C2-domain proteins like synaptotagmin (Syt)], the molecular mechanism of Ca2+-dependent release has been unclear. Here, we report that the Ca2+-sensitive oligomers of Syt1, a conserved structural feature among several C2-domain proteins, play a critical role in orchestrating Ca2+-coupled vesicular release. This follows from pHluorin-based imaging of single-vesicle exocytosis in pheochromocytoma (PC12) cells showing that selective disruption of Syt1 oligomerization using a structure-directed mutation (F349A) dramatically increases the normally low levels of constitutive exocytosis to effectively occlude Ca2+-stimulated release. We propose a parsimonious model whereby Ca2+-sensitive oligomers of Syt (or a similar C2-domain protein) assembled at the site of docking physically block spontaneous fusion until disrupted by Ca2+ Our data further suggest Ca2+-coupled vesicular release is triggered by removal of the inhibition, rather than by direct activation of the fusion machinery. |
| 巻・号 | 115(32) |
| ページ | E7624-E7631 |
| 公開日 | 2018-8-7 |
| DOI | 10.1073/pnas.1808792115 |
| PII | 1808792115 |
| PMID | 30038018 |
| PMC | PMC6094142 |
| MeSH | Animals Calcium / metabolism* Cations, Divalent / metabolism Cytoplasmic Vesicles / metabolism Cytoplasmic Vesicles / ultrastructure Exocytosis* Fluorescent Antibody Technique Green Fluorescent Proteins / chemistry Membrane Fusion / physiology* Microscopy, Electron Mutation PC12 Cells Protein Binding / physiology Protein Multimerization / physiology* Rats Recombinant Proteins / metabolism Synaptotagmin I / genetics Synaptotagmin I / metabolism* Vesicle-Associated Membrane Protein 2 / metabolism |
| IF | 9.412 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 2 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | PC12-F7(RCB2800) |