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Rebuilding essential active zone functions within a synapse
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DOI：10.1016/j.neuron.2022.01.026.png)
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Abstract
En 中文
Presynaptic active zones are molecular machines that control neurotransmitter secretion. They form sites for vesicle docking and priming and couple vesicles to Ca2+ entry for release triggering. The complexity of active zone machinery has made it challenging to determine its mechanisms in release. Simultaneous knockout of the active zone proteins RIM and ELKS disrupts active zone assembly, abolishes vesicle docking, and impairs release. We here rebuild docking, priming, and Ca2+ secretion coupling in these mutants without reinstating active zone networks. Re-expression of RIM zinc fingers recruited Munc13 to undocked vesicles and rendered the vesicles release competent. Action potential triggering of release was reconstituted by docking these primed vesicles to Ca2+ channels through attaching RIM zinc fingers to CaV beta 4-subunits. Our work identifies an 80-kDa beta 4-Zn protein that bypasses the need for megadalton-sized secretory machines, establishes that fusion competence and docking are mechanistically separable, and defines RIM zinc finger-Munc13 complexes as hubs for active zone function.
Keywords:
READILY RELEASABLE POOL
PRESYNAPTIC CA2+ CHANNELS
NEUROTRANSMITTER RELEASE
CALCIUM-CHANNELS
VESICLE DOCKING
RIM
PROTEIN
FUSION
GENE
LOCALIZATION
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