Cholesterol regulates multiple forms of vesicle endocytosis at a mammalian central synapse

Hai Yuan Yue, Jianhua Xu

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Endocytosis in synapses sustains neurotransmission by recycling vesicle membrane and maintaining the homeostasis of synaptic membrane. A role of membrane cholesterol in synaptic endocytosis remains controversial because of conflicting observations, technical limitations in previous studies, and potential interference from non-specific effects after cholesterol manipulation. Furthermore, it remains unclear whether cholesterol participates in distinct forms of endocytosis that function under different activity levels. In this study, applying the whole-cell membrane capacitance measurement to monitor endocytosis in real time at the rat calyx of Held terminals, we found that disrupting cholesterol with dialysis of cholesterol oxidase or methyl-β-cyclodextrin impaired three different forms of endocytosis, including slow endocytosis, rapid endocytosis, and endocytosis of the retrievable membrane that exists at the surface before stimulation. The effects were observed when disruption of cholesterol was mild enough not to change Ca2+ channel current or vesicle exocytosis, indicative of stringent cholesterol requirement in synaptic endocytosis. Extracting cholesterol with high concentrations of methyl-β-cyclodextrin reduced exocytosis, mainly by decreasing the readily releasable pool and the vesicle replenishment after readily releasable pool depletion. Our study suggests that cholesterol is an important, universal regulator in multiple forms of vesicle endocytosis at mammalian central synapses.

Original languageEnglish (US)
Pages (from-to)247-260
Number of pages14
JournalJournal of Neurochemistry
Volume134
Issue number2
DOIs
StatePublished - Jul 1 2015

Keywords

  • cholesterol
  • endocytosis
  • membrane capacitance
  • synapse
  • vesicle

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Fingerprint Dive into the research topics of 'Cholesterol regulates multiple forms of vesicle endocytosis at a mammalian central synapse'. Together they form a unique fingerprint.

  • Cite this