Identification of an Inhibitory Mechanism for Synaptic Vesicle Endocytosis
Yalong Wang, Ying Zhu, Wanru Li, Shuxin Yan, Chao Li, et al.
(see pages 6230–6248)
Successful, sustained neurotransmission requires synaptic vesicle (SV) endocytosis. SV endocytosis recovers the membranes and proteins of vesicles so that they can be reused. Zhang and colleagues previously discovered that a type of synaptotagmin (Syt11) inhibits this process. This finding combined with its potential role in neurological disorders, including schizophrenia and Parkinson's disease, suggest that the maintenance of neurotransmission by Syt11 is critical for proper brain functioning. In this issue, Wang, Zhu, et al. used mice to provide new insights into the mechanism through which this protein works. The authors found that deletion of Syt11 from hippocampal neurons accelerated SV endocytosis and led to abnormal separation of membrane proteins in synapses. The authors also identified the primary target of Syt11 during SV endocytosis: endophilin A1, a membrane sculptor required for endocytosis. This inhibitory mechanism for SV endocytosis ensures that vesicles are not retrieved too quickly, safeguarding synaptic protein recycling. These data reveal the relationship between Syt11 signaling and healthy neuronal communication and point to potential novel molecular targets for treating disorders in which SV endocytosis is not properly regulated.
Myc-Syt11 partially colocalized with EndoA1 at presynaptic hippocampal terminals. Top right insert, An enlargement. Scale bar, 5 µm. Arrows indicate colocalized puncta. Scale bar, original images, 25 µm.
Footnotes
This Week in The Journal was written by Paige McKeon
