期刊
JOURNAL OF NEUROSCIENCE
卷 31, 期 13, 页码 4886-4895出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.5122-10.2011
关键词
-
资金
- NIDCD NIH HHS [P30 DC005983, R01 DC008595, R01DC8595] Funding Source: Medline
Cochlear inner hair cells (IHCs) use Ca2+-dependent exocytosis of glutamate to signal sound information. Otoferlin (Otof), a C-2 domain protein essential for IHC exocytosis and hearing, may serve as a Ca2+ sensor in vesicle fusion in IHCs that seem to lack the classical neuronal Ca2+ sensors synaptotagmin 1 (Syt1) and Syt2. Support for the Ca2+ sensor of fusion hypothesis for otoferlin function comes from biochemical experiments, but additional roles in late exocytosis upstream of fusion have been indicated by physiological studies. Here, we tested the functional equivalence of otoferlin and Syt1 in three neurosecretory model systems: auditory IHCs, adrenal chromaffin cells, and hippocampal neurons. Long- term and short- term ectopic expression of Syt1 in IHCs of Otof(-/-) mice by viral gene transfer in the embryonic inner ear and organotypic culture failed to rescue their Ca2+ influx- triggered exocytosis. Conversely, virally mediated overexpression of otoferlin did not restore phasic exocytosis in Syt1- deficient chromaffin cells or neurons but enhanced asynchronous release in the latter. We further tested exocytosis in Otof(-/-) hippocampal neurons and in Syt1(-/-) IHCs but found no deficits in vesicle fusion. Expression analysis of different synaptotagminisoforms indicated that Syt1andSyt2 are absentfrommatureIHCs. Ourdata argue againstasimple functional equivalence of the two C-2 domain proteins in exocytosis of IHC ribbon synapses, chromaffin cells, and hippocampal synapses.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据