A Synaptic Vesicle-Associated Ca2+ Channel Promotes Endocytosis and Couples Exocytosis to Endocytosis

Chi Kuang Yao, Yong Qi Lin, Cindy V. Ly, Tomoko Ohyama, Claire M. Haueter, Vera Y. Moiseenkova-Bell, Theodore G. Wensel, Hugo J. Bellen

Research output: Contribution to journalArticlepeer-review

96 Scopus citations

Abstract

Synaptic vesicle (SV) exo- and endocytosis are tightly coupled to sustain neurotransmission in presynaptic terminals, and both are regulated by Ca2+. Ca2+ influx triggered by voltage-gated Ca2+ channels is necessary for SV fusion. However, extracellular Ca2+ has also been shown to be required for endocytosis. The intracellular Ca2+ levels (<1 μM) that trigger endocytosis are typically much lower than those (>10 μM) needed to induce exocytosis, and endocytosis is inhibited when the Ca2+ level exceeds 1 μM. Here, we identify and characterize a transmembrane protein associated with SVs that, upon SV fusion, localizes at periactive zones. Loss of Flower results in impaired intracellular resting Ca2+ levels and impaired endocytosis. Flower multimerizes and is able to form a channel to control Ca2+ influx. We propose that Flower functions as a Ca2+ channel to regulate synaptic endocytosis and hence couples exo- with endocytosis.

Original languageEnglish
Pages (from-to)947-960
Number of pages14
JournalCell
Volume138
Issue number5
DOIs
StatePublished - Sep 4 2009

Keywords

  • CELLBIO
  • MOLNEURO
  • SIGNALING

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