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Complexins: Ubiquitously Expressed Presynaptic Regulators of SNARE-Mediated Synaptic Vesicle Fusion

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Molecular Mechanisms of Neurotransmitter Release

Part of the book series: Advances in Neurobiology ((NEUROBIOL,volume 33))

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Abstract

Neurotransmitter release is a spatially and temporally tightly regulated process, which requires assembly and disassembly of SNARE complexes to enable the exocytosis of transmitter-loaded synaptic vesicles (SVs) at presynaptic active zones (AZs). While the requirement for the core SNARE machinery is shared by most membrane fusion processes, SNARE-mediated fusion at AZs is uniquely regulated to allow very rapid Ca2+-triggered SV exocytosis following action potential (AP) arrival. To enable a sub-millisecond time course of AP-triggered SV fusion, synapse-specific accessory SNARE-binding proteins are required in addition to the core fusion machinery. Among the known SNARE regulators specific for Ca2+-triggered SV fusion are complexins, which are almost ubiquitously expressed in neurons. This chapter summarizes the structural features of complexins, models for their molecular interactions with SNAREs, and their roles in SV fusion.

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Abbreviations

AA:

Amino Acids

AH:

Accessory Helix

AP:

Action potential

AZ:

Active zone

[Ca2+]:

Ca2+ concentration

CAPS:

Calcium-dependent Activator Protein for Secretion

CH:

Central Helix

CTD:

C-Terminal Domain

CNS:

Central nervous system

Cplx:

Complexin protein

DKD:

Double-knockdown

DKO:

Double-knockout

dm:

Drosophila melanogaster

eEPSC:

Evoked excitatory postsynaptic current

eIPSC:

Evoked inhibitory postsynaptic current

IPL:

Inner plexiform layer

K D :

Equilibrium dissociation constant

KD:

Knockdown

KO:

Knockout

k off :

Dissociation rate constant

k on :

Association rate constant

mEPSC:

Miniature excitatory postsynaptic current

MNTB:

Medial Nucleus of the Trapezoid Body

MW:

Molecular Weight

NTD:

N-Terminal Domain

NMJ :

Neuromuscular junction

OPL:

Outer plexiform layer

PD:

Parkinson’s disease

RRP:

Readily releasable pool

shRNA:

Short hairpin RNA

SNAP25:

Synaptosomal-associated protein, 25 kDa

SNARE :

Soluble N-ethylmaleimide-sensitive factor attachment protein receptor

SNP:

Single nucleotide polymorphism

Stx:

Syntaxin

SV:

Synaptic vesicle

Syb:

Synaptobrevin

Syt:

Synaptotagmin

TKO:

Triple-knockout

UTR:

Untranslated region

VAMP:

Vesicle-Associated Membrane Protein

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Acknowledgments

We would like to thank Dr. Noa Lipstein for insightful comments. F.J.L.-M. was a fellow of the Alexander von Humboldt Foundation and is supported by the Serra Húnter Programme and by the Spanish Ministry of Science and Innovation. K.R. acknowledges support by the German Research Foundation (DFG, grant RE 4382/2-1).

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Authors and Affiliations

  1. Department of Pathology and Experimental Therapy, Institute of Neurosciences, University of Barcelona, L’Hospitalet de Llobregat, Barcelona, Spain

    Francisco José López-Murcia

  2. Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat, Barcelona, Spain

    Francisco José López-Murcia

  3. Department of Molecular Neurobiology, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany

    Kerstin Reim & Holger Taschenberger

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  1. Francisco José López-Murcia
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Correspondence to Francisco José López-Murcia , Kerstin Reim or Holger Taschenberger .

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  1. Department of Neuroscience, University of Connecticut School of Medicine, Farmington, CT, USA

    Zhao-Wen Wang

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López-Murcia, F.J., Reim, K., Taschenberger, H. (2023). Complexins: Ubiquitously Expressed Presynaptic Regulators of SNARE-Mediated Synaptic Vesicle Fusion. In: Wang, ZW. (eds) Molecular Mechanisms of Neurotransmitter Release. Advances in Neurobiology, vol 33. Springer, Cham. https://doi.org/10.1007/978-3-031-34229-5_10

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