SCAMP5 Plays a Critical Role in Synaptic Vesicle Endocytosis during High Neuronal Activity
- Haiyan Zhao1,2,
- Yoonju Kim1,2,3,
- Joohyun Park1,2,3,
- Daehun Park1,2,
- Sang-Eun Lee1,2,
- Iree Chang1, and
- Sunghoe Chang1,2,3,4
- 1Department of Physiology and Biomedical Sciences,
- 2Biomembrane Plasticity Research Center,
- 3Neuroscience Research Institute, Medical Research Center, and
- 4Bio-Max Institute, Seoul National University College of Medicine, Seoul, South Korea 110-799
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Author contributions: H.Z., Y.K., and S.C. designed research; H.Z., Y.K., J.P., D.P., S.-E.L., and I.C. performed research; H.Z., Y.K., J.P., D.P., S.-E.L., I.C., and S.C. analyzed data; H.Z., Y.K., I.C., and S.C. wrote the paper.
Abstract
Secretory carrier membrane protein 5 (SCAMP5), a recently identified candidate gene for autism, is brain specific and highly abundant in synaptic vesicles (SVs), but its function is currently unknown. Here, we found that knockdown (KD) of endogenous SCAMP5 by SCAMP5-specific shRNAs in cultured rat hippocampal neurons resulted in a reduction in total vesicle pool size as well as in recycling pool size, but the recycling/resting pool ratio was significantly increased. SCAMP5 KD slowed endocytosis after stimulation, but impaired it severely during strong stimulation. We also found that KD dramatically lowered the threshold of activity at which SV endocytosis became unable to compensate for the ongoing exocytosis occurring during a stimulus. Reintroducing shRNA-resistant SCAMP5 reversed these endocytic defects. Therefore, our results suggest that SCAMP5 functions during high neuronal activity when a heavy load is imposed on endocytosis. Our data also raise the possibility that the reduction in expression of SCAMP5 in autistic patients may be related to the synaptic dysfunction observed in autism.
- Received May 28, 2014.
- Revision received June 16, 2014.
- Accepted June 20, 2014.
- Copyright © 2014 the authors 0270-6474/14/3410085-11$15.00/0
