Complexin has a dual synaptic function as checkpoint protein in vesicle priming and as a promoter of vesicle fusion
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Complexin has a dual synaptic function as checkpoint protein in vesicle priming and as a promoter of vesicle fusion. / López-Murcia, Francisco José; Lin, Kun Han; Berns, Manon M.M.; Ranjan, Mrinalini; Lipstein, Noa; Neher, Erwin; Brose, Nils; Reim, Kerstin; Taschenberger, Holger.
I: Proceedings of the National Academy of Sciences of the United States of America, Bind 121, Nr. 15, e2320505121, 2024.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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T1 - Complexin has a dual synaptic function as checkpoint protein in vesicle priming and as a promoter of vesicle fusion
AU - López-Murcia, Francisco José
AU - Lin, Kun Han
AU - Berns, Manon M.M.
AU - Ranjan, Mrinalini
AU - Lipstein, Noa
AU - Neher, Erwin
AU - Brose, Nils
AU - Reim, Kerstin
AU - Taschenberger, Holger
N1 - Publisher Copyright: Copyright © 2024 the Author(s). Published by PNAS. This open access article is distributed under Creative Commons Attribution License 4.0 (CC BY).
PY - 2024
Y1 - 2024
N2 - 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.
AB - 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.
KW - calyx of Held
KW - numerical simulation
KW - short-term plasticity
KW - synaptic transmission
KW - synaptic vesicle priming
U2 - 10.1073/pnas.2320505121
DO - 10.1073/pnas.2320505121
M3 - Journal article
C2 - 38568977
AN - SCOPUS:85190086790
VL - 121
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 15
M1 - e2320505121
ER -
ID: 397343356