Miniatura

Fitxers

858404.pdf (2.8 MB)

Tipus de document

Article

Versió

Versió publicada

Data de publicació

2024-04-03

Llicència de publicació

cc by (c) López-Murcia, Francisco José et al., 2024
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/210340

Complexin has a dual synaptic function as checkpoint protein in vesicle priming and as a promoter of vesicle fusion

Títol de la revista

Autors

Director/Tutor

ISSN de la revista

Títol del volum

Recurs relacionat

https://doi.org/https://doi.org/10.1073/pnas.2320505121

Resum

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.

Matèries

Proteïnes, Proteïnes SNARE, Teixit nerviós, Neurotransmissió

Matèries (anglès)

Proteins, SNARE Proteins, Nerve tissue, Neural transmission

Citació

Col·leccions

Articles publicats en revistes (Patologia i Terapèutica Experimental)
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

Citació

LÓPEZ MURCIA, Francisco josé, LIN, Kun-han, BERNS, Manon m. m., RANJAN, Mrinalini, LIPSTEIN, Noa, NEHER, Erwin, BROSE, Nils, REIM, Kerstin, TASCHENBERGER, Holger. Complexin has a dual synaptic function as checkpoint protein in vesicle priming and as a promoter of vesicle fusion. _Proceedings of the National Academy of Sciences of the United States of America - PNAS_. 2024. Vol. 121, núm. 15. [consulta: 21 de gener de 2026]. ISSN: 0027-8424. [Disponible a: https://hdl.handle.net/2445/210340]

Exportar metadades

JSON - METS

Compartir registre