ELKS active zone proteins as multitasking scaffolds for secretion

Open Biology
Richard G Held, Pascal S Kaeser

Abstract

Synaptic vesicle exocytosis relies on the tethering of release ready vesicles close to voltage-gated Ca2+ channels and specific lipids at the future site of fusion. This enables rapid and efficient neurotransmitter secretion during presynaptic depolarization by an action potential. Extensive research has revealed that this tethering is mediated by an active zone, a protein dense structure that is attached to the presynaptic plasma membrane and opposed to postsynaptic receptors. Although roles of individual active zone proteins in exocytosis are in part understood, the molecular mechanisms that hold the protein scaffold at the active zone together and link it to the presynaptic plasma membrane have remained unknown. This is largely due to redundancy within and across scaffolding protein families at the active zone. Recent studies, however, have uncovered that ELKS proteins, also called ERC, Rab6IP2 or CAST, act as active zone scaffolds redundant with RIMs. This redundancy has led to diverse synaptic phenotypes in studies of ELKS knockout mice, perhaps because different synapses rely to a variable extent on scaffolding redundancy. In this review, we first evaluate the need for presynaptic scaffolding, and we then discuss how the ...Continue Reading

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Citations

Jun 14, 2020·The Journal of Biological Chemistry·Andrei V ChernovVeronica I Shubayev
Nov 6, 2018·Frontiers in Neuroanatomy·Tina Ghelani, Stephan J Sigrist
Mar 13, 2020·Nature Reviews. Neuroscience·Annette C Dolphin, Amy Lee
Aug 4, 2020·Neural Development·Vivian T ChouDavid Van Vactor
Nov 18, 2020·Molecular Cell·Xiandeng WuMingjie Zhang
Sep 11, 2019·Molecular Metabolism·Mica Ohara-ImaizumiToshihisa Ohtsuka
Jun 11, 2020·Cell Reports·Hajnalka NyitraiPascal S Kaeser
Oct 6, 2021·Cell Reports·Achmed MrestaniMila M Paul

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Methods Mentioned

BETA
electron microscopy
protein knockout
confocal microscopy
GTPase

Software Mentioned

MARCOIL
ELKS

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