title: SCAMP5 plays a critical role in synaptic vesicle endocytosis during high neuronal activity.
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.
authors: Department of Physiology and Biomedical Sciences, Biomembrane Plasticity Research Center.
authors: Haiyan
authors: H
authors: Zhao
authors: Department of Physiology and Biomedical Sciences, Biomembrane Plasticity Research Center, Neuroscience Research Institute, Medical Research Center, and.
authors: Yoonju
authors: Y
authors: Kim
authors: Department of Physiology and Biomedical Sciences, Biomembrane Plasticity Research Center, Neuroscience Research Institute, Medical Research Center, and.
authors: Joohyun
authors: J
authors: Park
authors: Department of Physiology and Biomedical Sciences, Biomembrane Plasticity Research Center.
authors: Daehun
authors: D
authors: Park
authors: Department of Physiology and Biomedical Sciences, Biomembrane Plasticity Research Center.
authors: Sang-Eun
authors: SE
authors: Lee
authors: Department of Physiology and Biomedical Sciences.
authors: Iree
authors: I
authors: Chang
authors: Department of Physiology and Biomedical Sciences, Biomembrane Plasticity Research Center, Neuroscience Research Institute, Medical Research Center, and Bio-Max Institute, Seoul National University College of Medicine, Seoul, South Korea 110-799 sunghoe@snu.ac.kr.
authors: Sunghoe
authors: S
authors: Chang
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D004705:Endocytosis / Q000235:genetics / Q000502:physiology*; D005260:Female; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006624:Hippocampus / Q000166:cytology / Q000502:physiology; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D061251:Primary Cell Culture; D051381:Rats; D017207:Rats, Sprague-Dawley; D013572:Synaptic Vesicles / Q000235:genetics / Q000502:physiology*
chemical_list: D002352:Carrier Proteins; D008565:Membrane Proteins; C540013:SCAMP5 protein, human
keywords: SCAMP5; neuronal activity; recycling pool; resting pool; synaptic vesicle endocytosis