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Title: | Complexin has a dual synaptic function as checkpoint protein in vesicle priming and as a promoter of vesicle fusion |
Author: | López Murcia, Francisco José Lin, Kun-Han Berns, Manon M. M. Ranjan, Mrinalini Lipstein, Noa Neher, Erwin Brose, Nils Reim, Kerstin Taschenberger, Holger |
Keywords: | Proteïnes Proteïnes SNARE Teixit nerviós Neurotransmissió Proteins SNARE Proteins Nerve tissue Neural transmission |
Issue Date: | 3-Apr-2024 |
Publisher: | National Academy of Sciences |
Abstract: | The presynaptic SNARE-complex regulator complexin (Cplx) enhances the fusogenicity of primed synaptic vesicles (SVs). Consequently, Cplx deletion impairs action potential-evoked transmitter release. Conversely, though, Cplx loss enhances spontaneous and delayed asynchronous release at certain synapse types. Using electrophysiology and kinetic modeling, we show that such seemingly contradictory transmitter release phenotypes seen upon Cplx deletion can be explained by an additional of Cplx in the control of SV priming, where its ablation facilitates the generation of a "faulty" SV fusion apparatus. Supporting this notion, a sequential two-step priming scheme, featuring reduced vesicle fusogenicity and increased transition rates into the faulty primed state, reproduces all aberrations of transmitter release modes and short-term synaptic plasticity seen upon Cplx loss. Accordingly, we propose a dual presynaptic function for the SNARE-complex interactor Cplx, one as a "checkpoint" protein that guarantees the proper assembly of the fusion machinery during vesicle priming, and one in boosting vesicle fusogenicity. |
Note: | Reproducció del document publicat a: https://doi.org/https://doi.org/10.1073/pnas.2320505121 |
It is part of: | Proceedings of the National Academy of Sciences of the United States of America - PNAS, 2024, vol. 121, num.15 |
URI: | http://hdl.handle.net/2445/210340 |
Related resource: | https://doi.org/https://doi.org/10.1073/pnas.2320505121 |
ISSN: | 0027-8424 |
Appears in Collections: | Articles publicats en revistes (Patologia i Terapèutica Experimental) Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
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