CaV1 and CaV2 calcium channels mediate the release of distinct pools of synaptic vesicles.

Autor:	Mueller BD; Howard Hughes Medical Institute, School of Biological Sciences, University of Utah, Salt Lake City, United States., Merrill SA; Howard Hughes Medical Institute, School of Biological Sciences, University of Utah, Salt Lake City, United States., Watanabe S; Howard Hughes Medical Institute, School of Biological Sciences, University of Utah, Salt Lake City, United States., Liu P; Department of Neuroscience, University of Connecticut Medical School, Farmington, United States., Niu L; Department of Neuroscience, University of Connecticut Medical School, Farmington, United States., Singh A; Howard Hughes Medical Institute, School of Biological Sciences, University of Utah, Salt Lake City, United States., Maldonado-Catala P; Department of Neurobiology, University of Utah, Salt Lake City, United States., Cherry A; Howard Hughes Medical Institute, School of Biological Sciences, University of Utah, Salt Lake City, United States., Rich MS; Howard Hughes Medical Institute, School of Biological Sciences, University of Utah, Salt Lake City, United States., Silva M; Howard Hughes Medical Institute, School of Biological Sciences, University of Utah, Salt Lake City, United States., Maricq AV; Department of Neurobiology, University of Utah, Salt Lake City, United States., Wang ZW; Department of Neuroscience, University of Connecticut Medical School, Farmington, United States., Jorgensen EM; Howard Hughes Medical Institute, School of Biological Sciences, University of Utah, Salt Lake City, United States.
Jazyk:	angličtina
Zdroj:	ELife [Elife] 2023 Feb 23; Vol. 12. Date of Electronic Publication: 2023 Feb 23.
DOI:	10.7554/eLife.81407
Abstrakt:	Activation of voltage-gated calcium channels at presynaptic terminals leads to local increases in calcium and the fusion of synaptic vesicles containing neurotransmitter. Presynaptic output is a function of the density of calcium channels, the dynamic properties of the channel, the distance to docked vesicles, and the release probability at the docking site. We demonstrate that at Caenorhabditis elegans neuromuscular junctions two different classes of voltage-gated calcium channels, CaV2 and CaV1, mediate the release of distinct pools of synaptic vesicles. CaV2 channels are concentrated in densely packed clusters ~250 nm in diameter with the active zone proteins Neurexin, α-Liprin, SYDE, ELKS/CAST, RIM-BP, α-Catulin, and MAGI1. CaV2 channels are colocalized with the priming protein UNC-13L and mediate the fusion of vesicles docked within 33 nm of the dense projection. CaV2 activity is amplified by ryanodine receptor release of calcium from internal stores, triggering fusion up to 165 nm from the dense projection. By contrast, CaV1 channels are dispersed in the synaptic varicosity, and are colocalized with UNC-13S. CaV1 and ryanodine receptors are separated by just 40 nm, and vesicle fusion mediated by CaV1 is completely dependent on the ryanodine receptor. Distinct synaptic vesicle pools, released by different calcium channels, could be used to tune the speed, voltage-dependence, and quantal content of neurotransmitter release. Competing Interests: BM, SM, SW, PL, LN, AS, PM, AC, MR, MS, AM, ZW, EJ No competing interests declared (© 2023, Mueller, Merrill et al.)
Databáze:	MEDLINE
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