Abstract
Synaptic vesicle retrieval is an essential process for continuous maintenance of neural information flow after synaptic transmission. Epsin1, originally identified as an EPS15-interacting protein, is a major component of clathrin-mediated endocytosis. However, the role of Epsin1 in synaptic vesicle endocytosis at CNS synapses remains elusive. Here, we showed significantly altered synaptic vesicle endocytosis in neurons transfected with shRNA targeting Epsin1 during/after neural activity. Endocytosis was effectively restored by introducing shRNA-insensitive Epsin1 into Epsin1-depleted neurons. Domain studies performed on neurons in which domain deletion mutants of Epsin1 were introduced after Epsin1 knockdown revealed that ENTH, CLAP, and NPFs are essential for synaptic vesicle endocytosis, whereas UIMs are not. Strikingly, the efficacy of the rate of synaptic vesicle retrieval (the “endocytic capacity”) was significantly decreased in the absence of Epsin1. Thus, Epsin1 is required for proper synaptic vesicle retrieval and modulates the endocytic capacity of synaptic vesicles.
Highlights
That upon depletion of Epsin[1], the kinetics of synaptic vesicle endocytosis is severely impaired
Since Epsin[1] is a known adaptor protein in clathrin-mediated endocytosis (CME), we examined whether the protein is enriched at presynaptic terminals in primary cultured hippocampal neurons with high levels of CME
Since its identification as an EPS15 binding partner, Epsin has been implicated in clathrin-mediated endocytosis in various cellular systems, including cancer cells[32,33,34] and developmental processes[35,36]
Summary
That upon depletion of Epsin[1], the kinetics of synaptic vesicle endocytosis is severely impaired. Following Epsin[1] depletion in neurons, replacement with deletion mutants of individual ENTH, CLAP, and NPFs domains, but not UIMs, of Epsin[1] led to post-stimulus synaptic vesicle retrieval. Endocytic capacity induced by various neural activities was significantly altered in Epsin[1] knockdown (Epsin[1] KD) neurons
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