A synaptic vesicle-associated Ca2+ channel promotes endocytosis and couples exocytosis to endocytosis

Cell. 2009 Sep 4;138(5):947-60. doi: 10.1016/j.cell.2009.06.033.


Synaptic vesicle (SV) exo- and endocytosis are tightly coupled to sustain neurotransmission in presynaptic terminals, and both are regulated by Ca(2+). Ca(2+) influx triggered by voltage-gated Ca(2+) channels is necessary for SV fusion. However, extracellular Ca(2+) has also been shown to be required for endocytosis. The intracellular Ca(2+) levels (<1 microM) that trigger endocytosis are typically much lower than those (>10 microM) needed to induce exocytosis, and endocytosis is inhibited when the Ca(2+) level exceeds 1 microM. 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 Ca(2+) levels and impaired endocytosis. Flower multimerizes and is able to form a channel to control Ca(2+) influx. We propose that Flower functions as a Ca(2+) channel to regulate synaptic endocytosis and hence couples exo- with endocytosis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium Channels / analysis
  • Calcium Channels / metabolism*
  • Drosophila Proteins / analysis
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / cytology
  • Drosophila melanogaster / metabolism*
  • Endocytosis*
  • Exocytosis*
  • Protein Isoforms / analysis
  • Protein Isoforms / metabolism
  • Synaptic Vesicles / chemistry
  • Synaptic Vesicles / metabolism*


  • Calcium Channels
  • Drosophila Proteins
  • Protein Isoforms
  • fwe protein, Drosophila