Formation of an endophilin-Ca2+ channel complex is critical for clathrin-mediated synaptic vesicle endocytosis

Yuan Chen, Lunbin Deng, Yuka Maeno-Hikichi, Meizan Lai, Shaohua Chang, Gong Chen, Ji Fang Zhang

Research output: Contribution to journalArticlepeer-review

91 Scopus citations

Abstract

A tight balance between synaptic vesicle exocytosis and endocytosis is fundamental to maintaining synaptic structure and function. Calcium influx through voltage-gated Ca2+ channels is crucial in regulating synaptic vesicle exocytosis. However, much less is known about how Ca 2+ regulates vesicle endocytosis or how the endocytic machinery becomes enriched at the nerve terminal. We report here a direct interaction between voltage-gated Ca2+ channels and endophilin, a key regulator of clathrin-mediated synaptic vesicle endocytosis. Formation of the endophlin-Ca2+ channel complex is Ca2+ dependent. The primary Ca2+ binding domain resides within endophilin and regulates both endophilin-Ca2+ channel and endophilin-dynamin complexes. Introduction into hippocampal neurons of a dominant-negative endophilin construct, which constitutively binds to Ca2+ channels, significantly reduces endocytosis-mediated uptake of FM 4-64 dye without abolishing exocytosis. These results suggest an important role for Ca 2+ channels in coordinating synaptic vesicle recycling by directly coupling to both exocytotic and endocytic machineries.

Original languageEnglish (US)
Pages (from-to)37-48
Number of pages12
JournalCell
Volume115
Issue number1
DOIs
StatePublished - Oct 3 2003

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

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