Unc13a

Summary

Gene Symbol: Unc13a
Description: unc-13 homolog A (C. elegans)
Alias: 2410078G03Rik, Munc13-1, protein unc-13 homolog A, unc13a
Species: mouse
Products:     Unc13a

Top Publications

  1. Augustin I, Rosenmund C, Sudhof T, Brose N. Munc13-1 is essential for fusion competence of glutamatergic synaptic vesicles. Nature. 1999;400:457-61 pubmed
  2. Rhee J, Betz A, Pyott S, Reim K, Varoqueaux F, Augustin I, et al. Beta phorbol ester- and diacylglycerol-induced augmentation of transmitter release is mediated by Munc13s and not by PKCs. Cell. 2002;108:121-33 pubmed
    ..Modulation of Munc13-1 activity by second messengers via the DAG/beta phorbol ester binding C(1) domain is essential for use-dependent alterations of synaptic efficacy and survival. ..
  3. Varoqueaux F, Sigler A, Rhee J, Brose N, Enk C, Reim K, et al. Total arrest of spontaneous and evoked synaptic transmission but normal synaptogenesis in the absence of Munc13-mediated vesicle priming. Proc Natl Acad Sci U S A. 2002;99:9037-42 pubmed
  4. Varoqueaux F, Sons M, Plomp J, Brose N. Aberrant morphology and residual transmitter release at the Munc13-deficient mouse neuromuscular synapse. Mol Cell Biol. 2005;25:5973-84 pubmed
    ..Thus, non-Munc13 priming proteins exist at this synapse or vesicle priming occurs in part spontaneously: i.e., without dedicated priming proteins in the release machinery. ..
  5. Basu J, Betz A, Brose N, Rosenmund C. Munc13-1 C1 domain activation lowers the energy barrier for synaptic vesicle fusion. J Neurosci. 2007;27:1200-10 pubmed
  6. Kalla S, Stern M, Basu J, Varoqueaux F, Reim K, Rosenmund C, et al. Molecular dynamics of a presynaptic active zone protein studied in Munc13-1-enhanced yellow fluorescent protein knock-in mutant mice. J Neurosci. 2006;26:13054-66 pubmed
    ..They demonstrate the usefulness of the knock-in approach in general and of Munc13-1-EYFP knock-in mice in particular for imaging synaptic protein dynamics. ..
  7. Duncan R, Betz A, Shipston M, Brose N, Chow R. Transient, phorbol ester-induced DOC2-Munc13 interactions in vivo. J Biol Chem. 1999;274:27347-50 pubmed
    ..This is the first direct in vivo demonstration of a protein-protein interaction between two presynaptic proteins and may represent a molecular basis for phorbol ester-dependent enhancement of exocytosis. ..
  8. Mori R, Ikematsu K, Kitaguchi T, Kim S, Okamoto M, Chiba T, et al. Release of TNF-? from macrophages is mediated by small GTPase Rab37. Eur J Immunol. 2011;41:3230-9 pubmed publisher
    ..Knockdown of Munc13-1 by siRNA significantly decreased TNF-? secretion. Taken together, these findings demonstrate that Rab37 interacts with Munc13-1 to control TNF-? secretion from activated macrophages. ..
  9. Wentzel C, Sommer J, Nair R, Stiefvater A, Sibarita J, Scheiffele P. mSYD1A, a mammalian synapse-defective-1 protein, regulates synaptogenic signaling and vesicle docking. Neuron. 2013;78:1012-23 pubmed publisher
    ..Thus, mSYD1A is a regulator of presynaptic release sites at central synapses. ..

More Information

Publications43

  1. Imig C, Min S, Krinner S, Arancillo M, Rosenmund C, Südhof T, et al. The morphological and molecular nature of synaptic vesicle priming at presynaptic active zones. Neuron. 2014;84:416-31 pubmed publisher
  2. Man K, Imig C, Walter A, Pinheiro P, Stevens D, Rettig J, et al. Identification of a Munc13-sensitive step in chromaffin cell large dense-core vesicle exocytosis. elife. 2015;4: pubmed publisher
    ..Our data demonstrate that the molecular steps of SV and LDCV priming are very similar while SV and LDCV docking mechanisms are distinct. ..
  3. Reimers S, Hartlage Rübsamen M, Brückner G, Rossner S. Formation of perineuronal nets in organotypic mouse brain slice cultures is independent of neuronal glutamatergic activity. Eur J Neurosci. 2007;25:2640-8 pubmed
    ..These results indicate that neuronal activity is required but that the glutamatergic system is not essential for PN development. ..
  4. Sakane A, Manabe S, Ishizaki H, Tanaka Okamoto M, Kiyokage E, Toida K, et al. Rab3 GTPase-activating protein regulates synaptic transmission and plasticity through the inactivation of Rab3. Proc Natl Acad Sci U S A. 2006;103:10029-34 pubmed
    ..Thus, Rab3 GAP regulates synaptic transmission and plasticity by limiting the amount of the GTP-bound form of Rab3A. ..
  5. Vardar G, Chang S, Arancillo M, Wu Y, Trimbuch T, Rosenmund C. Distinct Functions of Syntaxin-1 in Neuronal Maintenance, Synaptic Vesicle Docking, and Fusion in Mouse Neurons. J Neurosci. 2016;36:7911-24 pubmed publisher
    ..Therefore, our work provides insights into differential functions of Stx1 in neuronal maintenance and neurotransmission, with the latter explored further into its functions in vesicle docking and fusion. ..
  6. Hong W. SNAREs and traffic. Biochim Biophys Acta. 2005;1744:120-44 pubmed
    ..In the post-genomic era, a fairly complete list of "all" SNAREs in several organisms (including human) can now be made. This review aims to summarize the key properties and the mechanism of action of SNAREs in mammalian cells. ..
  7. Zhao S, Mugabo Y, Iglesias J, Xie L, Delghingaro Augusto V, Lussier R, et al. ?/?-Hydrolase domain-6-accessible monoacylglycerol controls glucose-stimulated insulin secretion. Cell Metab. 2014;19:993-1007 pubmed publisher
    ..Monoacylglycerol binds and activates the vesicle priming protein Munc13-1, thereby inducing insulin exocytosis. We propose saturated monoacylglycerol as a signal for GSIS and ABHD6 as a negative modulator of insulin secretion. ..
  8. Wang X, Hu B, Zieba A, Neumann N, Kasper Sonnenberg M, Honsbein A, et al. A protein interaction node at the neurotransmitter release site: domains of Aczonin/Piccolo, Bassoon, CAST, and rim converge on the N-terminal domain of Munc13-1. J Neurosci. 2009;29:12584-96 pubmed publisher
  9. Lipstein N, Verhoeven Duif N, Michelassi F, Calloway N, van Hasselt P, Pieńkowska K, et al. Synaptic UNC13A protein variant causes increased neurotransmission and dyskinetic movement disorder. J Clin Invest. 2017;127:1005-1018 pubmed publisher
    ..shown that this condition is associated with a rare, de novo Pro814Leu variant in the major human Munc13 paralog UNC13A (also known as Munc13-1)...
  10. Monaghan C, Nechiporuk T, Jeng S, McWeeney S, Wang J, Rosenfeld M, et al. REST corepressors RCOR1 and RCOR2 and the repressor INSM1 regulate the proliferation-differentiation balance in the developing brain. Proc Natl Acad Sci U S A. 2017;114:E406-E415 pubmed publisher
    ..Our findings indicate that an INSM1/RCOR1/2 complex controls the balance of proliferation and differentiation during brain development. ..
  11. Vogl C, Cooper B, Neef J, Wojcik S, Reim K, Reisinger E, et al. Unconventional molecular regulation of synaptic vesicle replenishment in cochlear inner hair cells. J Cell Sci. 2015;128:638-44 pubmed publisher
    ..We conclude that IHCs use an unconventional priming machinery that involves otoferlin. ..
  12. Parsaud L, Li L, Jung C, Park S, Saw N, Park S, et al. Calcium-dependent activator protein for secretion 1 (CAPS1) binds to syntaxin-1 in a distinct mode from Munc13-1. J Biol Chem. 2013;288:23050-63 pubmed publisher
    ..We also propose that the preferential binding of CAPS1 to open syntaxin-1 can contribute to the stabilization of the open state of syntaxin-1 during its transition from "closed" state to the SNARE complex formation. ..
  13. Lipstein N, Sakaba T, Cooper B, Lin K, Strenzke N, Ashery U, et al. Dynamic control of synaptic vesicle replenishment and short-term plasticity by Ca(2+)-calmodulin-Munc13-1 signaling. Neuron. 2013;79:82-96 pubmed publisher
  14. Lai Y, Choi U, Leitz J, Rhee H, Lee C, Altas B, et al. Molecular Mechanisms of Synaptic Vesicle Priming by Munc13 and Munc18. Neuron. 2017;95:591-607.e10 pubmed publisher
    ..Together, the physiological functions of Munc13 may be related to regulation of proper SNARE complex assembly. ..
  15. Hartlage Rübsamen M, Waniek A, Roßner S. Munc13 genotype regulates secretory amyloid precursor protein processing via postsynaptic glutamate receptors. Int J Dev Neurosci. 2013;31:36-45 pubmed publisher
    ..We conclude that organotypic brain slices cultures are a valuable tool for studying APP processing pathways in intact neuronal circuits and that neuronal activity is important for maintenance of the non-amyloidogenic APP processing. ..
  16. Burgalossi A, Jung S, Meyer G, Jockusch W, Jahn O, Taschenberger H, et al. SNARE protein recycling by ?SNAP and ?SNAP supports synaptic vesicle priming. Neuron. 2010;68:473-87 pubmed publisher
    ..Our analysis of ?- and ?SNAP deletion mutant neurons shows that the two NSF cofactors support synaptic vesicle priming by determining the availability of free SNARE components, particularly during phases of high synaptic activity. ..
  17. Rossner S, Fuchsbrunner K, Lange Dohna C, Hartlage Rübsamen M, Bigl V, Betz A, et al. Munc13-1-mediated vesicle priming contributes to secretory amyloid precursor protein processing. J Biol Chem. 2004;279:27841-4 pubmed
    ..We establish that, in addition to PKC, Munc13-1 significantly contributes to the regulation of secretory APP metabolism. ..
  18. Xie L, Zhu D, Gaisano H. Role of mammalian homologue of Caenorhabditis elegans unc-13-1 (Munc13-1) in the recruitment of newcomer insulin granules in both first and second phases of glucose-stimulated insulin secretion in mouse islets. Diabetologia. 2012;55:2693-2702 pubmed publisher
  19. Siksou L, Varoqueaux F, Pascual O, Triller A, Brose N, Marty S. A common molecular basis for membrane docking and functional priming of synaptic vesicles. Eur J Neurosci. 2009;30:49-56 pubmed publisher
    ..These results indicate that SV docking at the plasma membrane and functional priming are respective morphological and physiological manifestations of the same molecular process mediated by SNARE complexes and Munc13s. ..
  20. Kwan E, Xie L, Sheu L, Ohtsuka T, Gaisano H. Interaction between Munc13-1 and RIM is critical for glucagon-like peptide-1 mediated rescue of exocytotic defects in Munc13-1 deficient pancreatic beta-cells. Diabetes. 2007;56:2579-88 pubmed
    ..We had reported that haplodeficient Munc13-1(+/-) mouse islet beta-cells exhibited reduced insulin secretion, causing glucose intolerance. Munc13-1 binds Epac2 and Rim2, but their functional interactions remain unclear...
  21. Kawabe H, Mitkovski M, Kaeser P, Hirrlinger J, Opazo F, Nestvogel D, et al. ELKS1 localizes the synaptic vesicle priming protein bMunc13-2 to a specific subset of active zones. J Cell Biol. 2017;216:1143-1161 pubmed publisher
    ..Thus, synapse-specific interactions of different Munc13 isoforms with ELKS1 or RIMs are key determinants of the molecular and functional heterogeneity of presynaptic AZs. ..
  22. Kwan E, Xie L, Sheu L, Nolan C, Prentki M, Betz A, et al. Munc13-1 deficiency reduces insulin secretion and causes abnormal glucose tolerance. Diabetes. 2006;55:1421-9 pubmed
  23. Orenbuch A, Ayelet O, Shulman Y, Yoav S, Lipstein N, Noa L, et al. Inhibition of exocytosis or endocytosis blocks activity-dependent redistribution of synapsin. J Neurochem. 2012;120:248-58 pubmed publisher
    ..Our results therefore reveal hitherto unidentified feedback within the synaptic vesicle cycle involving the synapsin-managed reserve pool...
  24. van de Bospoort R, Farina M, Schmitz S, de Jong A, de Wit H, Verhage M, et al. Munc13 controls the location and efficiency of dense-core vesicle release in neurons. J Cell Biol. 2012;199:883-91 pubmed publisher
    ..Thus, Munc13-1/2 facilitate DCV fusion but, unlike for synaptic vesicles, are not essential for DCV release, and M13OE is sufficient to produce efficient DCV release extrasynaptically. ..
  25. Chen Z, Cooper B, Kalla S, Varoqueaux F, Young S. The Munc13 proteins differentially regulate readily releasable pool dynamics and calcium-dependent recovery at a central synapse. J Neurosci. 2013;33:8336-51 pubmed publisher
    ..Based on these data, we conclude that Munc13-2 and Munc13-3 isoforms limit the ability of Munc13-1 to regulate calcium-dependent replenishment of readily releasable pool and slow pool to fast pool conversion in central synapses. ..
  26. Heupel K, Sargsyan V, Plomp J, Rickmann M, Varoqueaux F, Zhang W, et al. Loss of transforming growth factor-beta 2 leads to impairment of central synapse function. Neural Dev. 2008;3:25 pubmed publisher
    ..The functional alterations in the respiratory center of the brain are probably the underlying cause of the perinatal death of the TGF-beta2 knock-out mice. ..
  27. Gerber S, Rah J, Min S, Liu X, de Wit H, Dulubova I, et al. Conformational switch of syntaxin-1 controls synaptic vesicle fusion. Science. 2008;321:1507-10 pubmed publisher
    ..Thus, the closed conformation of syntaxin-1 gates the initiation of the synaptic vesicle fusion reaction, which is then mediated by SNARE-complex/Munc18-1 assemblies. ..
  28. Lou X, Korogod N, Brose N, Schneggenburger R. Phorbol esters modulate spontaneous and Ca2+-evoked transmitter release via acting on both Munc13 and protein kinase C. J Neurosci. 2008;28:8257-67 pubmed publisher
    ..Thus, docked and readily releasable vesicles are a substrate for modulation via intracellular second-messenger pathways that act via Munc13 and PKC. ..
  29. Okamoto Y, Lipstein N, Hua Y, Lin K, Brose N, Sakaba T, et al. Distinct modes of endocytotic presynaptic membrane and protein uptake at the calyx of Held terminal of rats and mice. elife. 2016;5: pubmed publisher
    ..Our data identify a novel mechanism of stimulus- and Ca(2+)-dependent regulation of coordinated endocytosis of synaptic membranes and vesicle proteins. ..
  30. Rosenmund C, Sigler A, Augustin I, Reim K, Brose N, Rhee J. Differential control of vesicle priming and short-term plasticity by Munc13 isoforms. Neuron. 2002;33:411-24 pubmed
    ..Thus, differential expression of Munc13 isoforms at individual synapses represents a general mechanism that controls short-term plasticity and contributes to the heterogeneity of synaptic information coding. ..
  31. Sigler A, Oh W, Imig C, Altas B, Kawabe H, Cooper B, et al. Formation and Maintenance of Functional Spines in the Absence of Presynaptic Glutamate Release. Neuron. 2017;94:304-311.e4 pubmed publisher
  32. Kang L, He Z, Xu P, Fan J, Betz A, Brose N, et al. Munc13-1 is required for the sustained release of insulin from pancreatic beta cells. Cell Metab. 2006;3:463-8 pubmed
    ..Our data show that Munc13-1 plays an essential role in the development of the second phase of insulin secretion by priming insulin-containing LDCVs. ..
  33. Tada H, Okano H, Takagi H, Shibata S, Yao I, Matsumoto M, et al. Fbxo45, a novel ubiquitin ligase, regulates synaptic activity. J Biol Chem. 2010;285:3840-9 pubmed publisher
    ..We also found that Fbxo45 induces the degradation of a synaptic vesicle-priming factor, Munc13-1. We propose that Fbxo45 plays an important role in the regulation of neurotransmission by modulating Munc13-1 at the synapse. ..
  34. Lipstein N, Schaks S, Dimova K, Kalkhof S, Ihling C, Kölbel K, et al. Nonconserved Ca(2+)/calmodulin binding sites in Munc13s differentially control synaptic short-term plasticity. Mol Cell Biol. 2012;32:4628-41 pubmed publisher