ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2008
Vesicle priming and recruitment by ubMunc13-2 are differentially regulated by calcium and calmodulin.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 55 citations in OpenAlex.
- Dynamic regulation of vesicle pools in a detailed spatial model of the complete synaptic vesicle cycle.Science advances · 2025Article
- Control of Munc13-1 Activity by Autoinhibitory Interactions Involving the Variable N-terminal Region.Journal of molecular biology · 2024Article
- Control of Munc13-1 Activity by Autoinhibitory Interactions Involving the Variable N-terminal Region.bioRxiv : the preprint server for biology · 2024Article
- Association of the risk factorFrontiers in aging neuroscience · 2023Article
- Phorbolester-activated Munc13-1 and ubMunc13-2 exert opposing effects on dense-core vesicle secretion.eLife · 2022Article
- The role of snare proteins in cortical development.Developmental neurobiology · 2022Review
- Munc13-1 is a CaNeuron · 2021Article
- Synaptotagmin-7 places dense-core vesicles at the cell membrane to promote Munc13-2- and CaeLife · 2021Article
- The Polarized Redistribution of the Contractile Vacuole to the Rear of the Cell is Critical for Streaming and is Regulated by PI(4,5)P2-Mediated Exocytosis.Frontiers in cell and developmental biology · 2021Review
- The Role of Calmodulin vs. Synaptotagmin in Exocytosis.Frontiers in molecular neuroscience · 2021Review
- Article
- Neurosecretion: what can we learn from chromaffin cells.Pflugers Archiv : European journal of physiology · 2018Review
- Doc2B acts as a calcium sensor for vesicle priming requiring synaptotagmin-1, Munc13-2 and SNAREs.eLife · 2017Article
- Frequency-dependent mobilization of heterogeneous pools of synaptic vesicles shapes presynaptic plasticity.eLife · 2017Article
- Heterodimerization of Munc13 CNature communications · 2017Article
- ELKS1 localizes the synaptic vesicle priming protein bMunc13-2 to a specific subset of active zones.The Journal of cell biology · 2017Article
- Identification of a Munc13-sensitive step in chromaffin cell large dense-core vesicle exocytosis.eLife · 2015Article
- Vesicle Motion during Sustained Exocytosis in Chromaffin Cells: Numerical Model Based on Amperometric Measurements.PloS one · 2015Article
- Calmodulin enhances ribbon replenishment and shapes filtering of synaptic transmission by cone photoreceptors.The Journal of general physiology · 2014Article
- Association analysis of four candidate genetic variants with sporadic amyotrophic lateral sclerosis in a Chinese population.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2014Article
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Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ca2+ regulates multiple processes in nerve terminals, including synaptic vesicle recruitment, priming, and fusion. Munc13s, the mammalian homologs of Caenorhabditis elegans Unc13, are essential vesicle-priming proteins and contain multiple regulatory domains that bind second messengers such as diacylglycerol and Ca2+/calmodulin (Ca2+/CaM). Binding of Ca2+/CaM is necessary for the regulatory effect that allows Munc13-1 and ubMunc13-2 to promote short-term synaptic plasticity. However, the relative contributions of Ca2+ and Ca2+/CaM to vesicle priming and recruitment by Munc13 are not known. Here, we investigated the effect of Ca2+/CaM binding on ubMunc13-2 activity in chromaffin cells via membrane-capacitance measurements and a detailed simulation of the exocytotic machinery. Stimulating secretion under various basal Ca2+ concentrations from cells overexpressing either ubMunc13-2 or a ubMunc13-2 mutant deficient in CaM binding enabled a distinction between the effects of Ca2+ and Ca2+/CaM. We show that vesicle priming by ubMunc13-2 is Ca2+ dependent but independent of CaM binding to ubMunc13-2. However, Ca2+/CaM binding to ubMunc13-2 specifically promotes vesicle recruitment during ongoing stimulation. Based on the experimental data and our simulation, we propose that ubMunc13-2 is activated by two Ca2+-dependent processes: a slow activation mode operating at low Ca2+ concentrations, in which ubMunc13-2 acts as a priming switch, and a fast mode at high Ca2+ concentrations, in which ubMunc13-2 is activated in a Ca2+/CaM-dependent manner and accelerates vesicle recruitment and maturation during stimulation. These different Ca2+ activation steps determine the kinetic properties of exocytosis and vesicle recruitment and can thus alter plasticity and efficacy of transmitter release.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.