A synaptic vesicle-associated Ca2+ channel promotes endocytosis and couples exocytosis to endocytosis.
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.
Yao
Chi-Kuang
CK
Howard Hughes Medical Institute, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Lin
Yong Qi
YQ
Ly
Cindy V
CV
Ohyama
Tomoko
T
Haueter
Claire M
CM
Moiseenkova-Bell
Vera Y
VY
Wensel
Theodore G
TG
Bellen
Hugo J
HJ
D000818:Animals; D015220:Calcium Channels / Q000032:analysis / Q000378:metabolism*; D029721:Drosophila Proteins / Q000032:analysis / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology / Q000378:metabolism*; D004705:Endocytosis; D005089:Exocytosis; D020033:Protein Isoforms / Q000032:analysis / Q000378:metabolism; D013572:Synaptic Vesicles / Q000737:chemistry / Q000378:metabolism*
D015220:Calcium Channels; D029721:Drosophila Proteins; D020033:Protein Isoforms; C543900:fwe protein, Drosophila