Vesicular sterols are essential for synaptic vesicle cycling

Document Type

Article

Publication Title

Journal of Neuroscience

Publication Date

11-24-2010

Volume

30

Issue

47

First Page

15856

Last Page

15865

DOI

10.1523/JNEUROSCI.4132-10.2010

ISSN

02706474

Abstract

Synaptic vesicles have a high sterol content, but the importance of vesicular sterols during vesicle recycling is unclear. We used the Drosophila temperature-sensitive dynamin mutant, shibire-ts1, to block endocytosis of recycling synaptic vesicles and to trap them reversibly at the plasma membrane where they were accessible to sterol extraction. Depletion of sterols from trapped vesicles prevented recovery of synaptic transmission after removal of the endocytic block. Measurement of vesicle recycling with synaptopHluorin, FM1-43, and FM4-64 demonstrated impaired membrane retrieval after vesicular sterol depletion. When plasma membrane sterols were extracted before vesicle trapping, no vesicle recycling defects were observed. Ultrastructural analysis indicated accumulation of endosomes and a defect in the formation of synaptic vesicles in synaptic terminals subjected to vesicular sterol depletion. Our results demonstrate the importance of a high vesicular sterol concentration for endocytosis and suggest that vesicular and membrane sterol pools do not readily intermingle during vesicle recycling. Copyright © 2010 the authors.

E-ISSN

15292401

PubMed ID

21106824

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