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

CK Yao, YQ Lin, CV Ly, T Ohyama, CM Haueter… - Cell, 2009 - cell.com
CK Yao, YQ Lin, CV Ly, T Ohyama, CM Haueter, VY Moiseenkova-Bell, TG Wensel
Cell, 2009cell.com
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 μM) that
trigger endocytosis are typically much lower than those (> 10 μM) needed to induce
exocytosis, and endocytosis is inhibited when the Ca 2+ level exceeds 1 μM. Here, we …
Summary
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.
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