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Abnormal splicing mutation in UNC13B was identified in the patient with bipolar disorder.
Assisted by NSF/alpha-SNAP, syntaxin-1 escapes tomosyn arrest and assembles into the Munc18-1/syntaxin-1 complex. Munc13-1 then catalyzes the transit of syntaxin-1 from the Munc18-1/syntaxin-1 complex to the SNARE complex
A rare missense variation (V1525M) in UNC13B was identified by WES in the multiplex family; this variation was present in five of six affected individuals, but not in eight unaffected individuals or one individual of unknown disease status. Resequencing UNC13B coding regions identified five rare missense variations (T103M, M813T, P1349T, I1362T, and V1525M).
The 1-5-8-26 CaM binding motif discovered in Munc13-1 cannot be induced in the classical CaM target skMLCK, indicating unique features of the Munc13 CaM binding motif.
Munc13-1 regulates insulin exocytosis
MUNC13-4 mutations play a role in the development of familial haemophagocytic lymphohistiocytosis subtype 3 through a defective cytotoxic pathway
Data suggest that diacylglycerol-activated hmunc13 serves as an effector of Rab34, mediating lysosome-Golgi trafficking.
Data identified a polymorphism in the UNC13B gene associated with nephropathy. UNC13B mediates apopotosis in glomerular cells in the presence of hyperglycemia, an event occurring early in the development of nephropathy.
In the bound state, the hydrophobic anchor residue of the calmodulin (CaM)-binding motif in Munc13 contacts two distinct methionine residues in the carboxyl-terminal domain of CaM.
mechanistic basis for high glucose-induced protein secretion is through interaction of munc13 and rab34, indicating a potentially critical role for this newly described pathway in the pathogenesis of DN.
Chromaffin cell vesicle-priming by brain-specific ubMunc13 isoform 2 is calcium ion (Ca2+) dependent but independent of calmodulin binding to ubMunc13 isoform 2.
Munc13-1 and Munc18-1, but not CAPS-1/2, stabilize primed synaptic vesicles by preventing NSF-dependent de-priming.
Data suggest that the Munc13-1/2 heterodimer is an active component of the vesicle docking, priming and release complex.
In a model of systemic anaphylaxis, we found no difference between WT and Munc13-2 KO mice, but global and mast cells-specific Munc13-4 KO mice developed less hypothermia. We conclude that although Munc13-2 plays a minor role, Munc13-4 is essential for regulated exocytosis in mast cells
Mutating Ca(2+)-coordinating aspartates in the C2A-domain localizes Doc2B permanently at the plasma membrane, and renders an upstream priming step Ca(2+)-independent, whereas a separate function in downstream priming depends on SNARE-binding, Ca(2+)-binding to the C2B-domain of Doc2B, interaction with ubMunc13-2 and the presence of synaptotagmin-1.
This study characterizes Munc13-1 as a target of resveratrol and highlights the importance of dietary polyphenol in the management of neurodegenerative diseases
SIGNIFICANCE STATEMENT: DBA/2J and C57BL/6J mice have been used to understand the genetic mechanisms controlling behaviors related to a number of psychiatric illnesses. However, the fundamental neurobiological mechanisms producing these behavioral characteristics remain unresolved. Here we identify a critical family of presynaptic proteins differentially expressed by these strains that control strain-dependent synaptic ph
Munc13-2 is recruited to synapses by the AZ protein ELKS1.
Munc13-2 plays a fundamental role in large dense-core vesicle exocytosis, but in contrast to synapses lacking Munc13s, the corresponding chromaffin cells do not exhibit a vesicle docking defect.
Data demonstrate that Munc13-1 and DOC2B have different effects on network activity and that by enhancing asynchronous release, DOC2B exerts its properties to increase spiking activity and elevate synchronization between neurons within network bursts
Munc13-1 isoform is functionaly redundant in cytotoxic T lymphocytes.
betaARs couple to a cAMP/Epac/PLC/Munc13-1/Rab3a/RIM1a-dependent pathway to enhance glutamate release at cerebrocortical nerve terminals.
Our data establish Munc13-1 as a major presynaptic target of Ca(2+)-Calmodulin signaling and show that the Ca(2+)-Calmodulin-Munc13-1 complex is a pivotal component of the molecular machinery that determines short-term synaptic plasticity characteristics.
The Munc13 gene family encodes molecules located at the synaptic active zone that regulate the reliability of synapses to encode information over a wide range of frequencies in response to action potentials.
This study demonistrated that Munc13 genotype regulates secretory amyloid precursor protein processing via postsynaptic glutamate receptors
Mammalian homologue of Caenorhabditis elegans unc-13-1 (Munc13-1) plays a role in the recruitment of newcomer insulin granules in both first and second phases of glucose-stimulated insulin secretion in mouse islets.
Munc13-1/2 were shown to facilitate dense-core vesicle fusion but, unlike for synaptic vesicles, were not essential for dense-core vesicle release.
The composition of Munc13 isoforms in a neuron differentially controls its short-term synaptic plasticity characteristics.
photoreceptor ribbon synapses and conventional synapses differ fundamentally with regard to their dependence on synaptic vesicles priming proteins of the Munc13 family
Disruption of Munc13-1 function inhibits mossy fiber long-term potentiation
Data show that homodimerization of Munc13 inhibits its synaptic vesicle priming function, and RIMs activate priming by disrupting Munc13 homodimerization.
This gene is expressed in the kidney cortical epithelial cells and is upregulated by hyperglycemia. The encoded protein shares a high level of similarity to the rat homolog, and contains 3 C2 domains and a diacylglycerol-binding C1 domain. Hyperglycemia increases the levels of diacylglycerol, which has been shown to induce apoptosis in cells transfected with this gene and thus contribute to the renal cell complications of hyperglycemia. Studies in other species also indicate a role for this protein in the priming step of synaptic vesicle exocytosis.
homolog of rat Munc13 (diacylglycerol-binding)
, protein unc-13 homolog B
, unc-13 homolog B (C. elegans)
, unc-13 B-like protein
, UNC-13 homolog 1
, unc-13 homolog A
, unc13 homolog 1
, protein unc-13 homolog B-like