Synaptotagmin-11 inhibits neuronal endocytosis

What is it about?

Neurons often communicate with other cells through releasing neurotransmitters packed in vesicles. These vesicles fuse with the plasma membrane to release their cargo and then both the lipid and protein components of these vesicles need to be retrieved by endocytosis for future reuse. Regulation of endocytosis has been extensively studied in the past four decades but inhibitors have rarely been found. This paper reports an inhibitor, synaptotagmin 11 (Syt11, a candidate gene for susceptibility to schizophrenia and a risk locus for Parkinson disease), for two major forms of neuronal endocytosis—clathrin-mediated and bulk endocytosis. We discover that Syt11 specifically inhibited the initiation of endocytosis without affecting later steps of the process.

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Why is it important?

When neurons are highly active, robust vesicle fusion occurs and the demand for precise and efficient endocytosis is also high in order to keep up with the vesicle cycle. While neuronal endocytosis has been extensively studied, mechanisms to ensure the precision and fidelity of vesicle retrieval remain elusive. We propose that Syt11 may function to ensure precision in vesicle retrieval and disruption of this inhibitory mechanism may partake in certain brain diseases such as Parkinson disease and schizophrenia.

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