Unc13b

Summary

Gene Symbol: Unc13b
Description: unc-13 homolog B (C. elegans)
Alias: Munc13-1, Munc13-2, Unc13a, Unc13h1, Unc13h2, protein unc-13 homolog B, UNC-13 homolog 1, munc13, unc-13 homolog A, unc13 homolog 1
Species: mouse
Products:     Unc13b

Top Publications

  1. 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
    b>Munc13-1 is a presynaptic protein with an essential role in synaptic vesicle priming...
  2. Deng L, Kaeser P, Xu W, Sudhof T. RIM proteins activate vesicle priming by reversing autoinhibitory homodimerization of Munc13. Neuron. 2011;69:317-31 pubmed publisher
    ..In particular, the Zn²+ finger domain of RIMs binds to the C?A domain of the priming factor Munc13, which forms a homodimer in the absence of RIM but a heterodimer with it...
  3. 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
    ..Essential vesicle priming proteins of the Munc13 (mammalian Unc13) family play an important role in adapting vesicle supply to variable demand and thus influence ..
  4. 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
    ..The presynaptic active zone protein Munc13-1 is essential for priming of glutamatergic synaptic vesicles in hippocampal neurons...
  5. 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
    ..Here we identify Munc13-1, a brain-specific presynaptic phorbol ester receptor, as an essential protein for synaptic vesicle maturation...
  6. Gioia D, Alexander N, McCool B. Differential Expression of Munc13-2 Produces Unique Synaptic Phenotypes in the Basolateral Amygdala of C57BL/6J and DBA/2J Mice. J Neurosci. 2016;36:10964-10977 pubmed
    ..2011) identified a segment on chromosome 4 containing the gene encoding Munc13-2, which has calcium-/phorbol ester-binding domains and controls presynaptic function...
  7. 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
    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...
  8. Pany S, Ghosh A, You Y, Nguyen N, Das J. Resveratrol inhibits phorbol ester-induced membrane translocation of presynaptic Munc13-1. Biochim Biophys Acta Gen Subj. 2017;1861:2640-2651 pubmed publisher
    ..Resveratrol inhibits PKCα by binding to its activator-binding C1 domain. Munc13-1 is a C1 domain-containing Ca2+-sensitive SNARE complex protein essential for vesicle priming and ..
  9. 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

More Information

Publications46

  1. 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
    ..neuroendocrine and immune cells, vesicle replenishment depends on proteins of the mammalian uncoordinated 13 (Munc13, also known as Unc13) and Ca(2+)-dependent activator proteins for secretion (CAPS) families, which prime vesicles ..
  2. 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
    ..active zone recruitment (tethering) and membrane attachment (docking) and found that vesicle docking requires Munc13/CAPS family priming proteins and all three neuronal SNAREs, but not Synaptotagmin-1 or Complexins...
  3. Ferrero J, Alvarez A, Ramírez Franco J, Godino M, Bartolomé Martín D, Aguado C, et al. ?-Adrenergic receptors activate exchange protein directly activated by cAMP (Epac), translocate Munc13-1, and enhance the Rab3A-RIM1? interaction to potentiate glutamate release at cerebrocortical nerve terminals. J Biol Chem. 2013;288:31370-85 pubmed publisher
    ..Epac activation translocated the active zone protein Munc13-1 from soluble to particulate fractions; it increased the association between Rab3A and RIM1? and redistributed ..
  4. 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
    ..We studied calyces of Held in knockin mice that express a Ca(2+)-Calmodulin insensitive Munc13-1(W464R) variant of the synaptic vesicle priming protein Munc13-1...
  5. Dudenhöffer Pfeifer M, Schirra C, Pattu V, Halimani M, Maier Peuschel M, Marshall M, et al. Different Munc13 isoforms function as priming factors in lytic granule release from murine cytotoxic T lymphocytes. Traffic. 2013;14:798-809 pubmed publisher
    ..In secretory tissues such as brain and neuroendocrine glands, this process is mediated by members of the Munc13 protein family...
  6. 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
    ..Previously, we have identified the presynaptic protein Munc13-1 as a diacylglycerol/phorbolester (DAG/PE) receptor that contributes to secretory, non-amyloidogenic APP ..
  7. 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
    ..During high synaptic activity, Munc13-1 and its closely related homolog, ubMunc13-2, bind Ca(2+)/calmodulin, resulting in enhanced priming activity and ..
  8. Houy S, Groffen A, Ziomkiewicz I, Verhage M, Pinheiro P, Sørensen J. Doc2B acts as a calcium sensor for vesicle priming requiring synaptotagmin-1, Munc13-2 and SNAREs. elife. 2017;6: pubmed publisher
    Doc2B is a cytosolic protein with binding sites for Munc13 and Tctex-1 (dynein light chain), and two C2-domains that bind to phospholipids, Ca2+ and SNAREs...
  9. Sheu L, Pasyk E, Ji J, Huang X, Gao X, Varoqueaux F, et al. Regulation of insulin exocytosis by Munc13-1. J Biol Chem. 2003;278:27556-63 pubmed
    ..b>Munc13-1, a synaptic protein that regulates SNARE complex assembly, is the major protein determining the priming of ..
  10. 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
    ..b>Munc13-1, a presynaptic protein with an essential role in synaptic vesicle priming, represents such an alternative target ..
  11. Breustedt J, Gundlfinger A, Varoqueaux F, Reim K, Brose N, Schmitz D. Munc13-2 differentially affects hippocampal synaptic transmission and plasticity. Cereb Cortex. 2010;20:1109-20 pubmed publisher
    ..Here, we found that a member of the Munc13 protein family of priming proteins, namely Munc13-2, is essential for normal release probability at hippocampal ..
  12. 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
    ..esters strongly potentiate transmitter release at synapses by activating protein kinase C (PKC) and members of the Munc13 family of presynaptic vesicle priming proteins...
  13. Zhu Y, Ehre C, Abdullah L, Sheehan J, Roy M, Evans C, et al. Munc13-2-/- baseline secretion defect reveals source of oligomeric mucins in mouse airways. J Physiol. 2008;586:1977-92 pubmed publisher
    ..sensitization, it was surprising to find that the lungs of mice deficient for the exocytic priming protein Munc13-2 stain prominently with AB/PAS under control conditions...
  14. 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...
  15. 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
    ..and functionally unique axonal subpopulations of synapses in excitatory hippocampal neurons that utilize either Munc13-1 or Munc13-2 as synaptic vesicle priming factor...
  16. 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
    ..We show that particularly Munc13-2 plays a fundamental role in LDCV exocytosis, but in contrast to synapses lacking Munc13s, the corresponding ..
  17. 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. ..
  18. 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
    ..synaptogenesis and neurotransmitter release of mice lacking all synaptic vesicle priming proteins of the Munc13 family...
  19. Lavi A, Sheinin A, Shapira R, Zelmanoff D, Ashery U. DOC2B and Munc13-1 differentially regulate neuronal network activity. Cereb Cortex. 2014;24:2309-23 pubmed publisher
    ..pharmacological tools and genetic manipulation of synaptic proteins, we show that overexpression of DOC2B and Munc13-1, proteins known to promote vesicular maturation and release, elicits opposite effects on the activity of the ..
  20. 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
    ..DCVs also fused at extrasynaptic sites but only after prolonged stimulation. In munc13-1/2-null mutant neurons, synaptic DCV release was reduced but not abolished, and synaptic preference was lost...
  21. 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
    We have previously reported that the haplodeficient Munc13-1(+/-) mouse exhibits impaired biphasic glucose-stimulated insulin secretion (GSIS), causing glucose intolerance mimicking type 2 diabetes...
  22. Broeke J, Roelandse M, Luteijn M, Boiko T, Matus A, Toonen R, et al. Munc18 and Munc13 regulate early neurite outgrowth. Biol Cell. 2010;102:479-88 pubmed publisher
    ..secretion, such as SNARE (soluble N-ethylmaleimide-sensitive fusion protein-attachment protein receptor) proteins, Munc13 and Munc18...
  23. 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. ..
  24. 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
    ..Vesicle fusion is preceded by an obligatory Munc13-dependent priming process that conveys fusion competence to SVs by facilitating SNARE complex assembly...
  25. Kasmapour B, Gronow A, Bleck C, Hong W, Gutierrez M. Size-dependent mechanism of cargo sorting during lysosome-phagosome fusion is controlled by Rab34. Proc Natl Acad Sci U S A. 2012;109:20485-90 pubmed publisher
    ..Here, we show a specific role for Rab34 and mammalian uncoordinated 13-2 (Munc13-2) in phagolysosome biogenesis and cargo delivery...
  26. Andrews Zwilling Y, Kawabe H, Reim K, Varoqueaux F, Brose N. Binding to Rab3A-interacting molecule RIM regulates the presynaptic recruitment of Munc13-1 and ubMunc13-2. J Biol Chem. 2006;281:19720-31 pubmed
    ..We show here that the active zone recruitment of Munc13 isoforms Munc13-1 and ubMunc13-2 is regulated by their binding to the Rab3A-interacting molecule RIM1alpha, a key ..
  27. Polinsky C, Houston C, Vado J, Shaikh A, Kohn R. Synaptic protein UNC-13 interacts with an F-box protein that may target it for degradation by proteasomes. Acta Biochim Pol. 2006;53:145-8 pubmed
    ..Yeast assays also identified an exonuclease, a predicted splicing factor, and a protein with coiled-coil domains, indicating that UNC-13 may affect RNA function. ..
  28. 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
    ..that blockage of exocytosis in cultured mouse hippocampal neurons, either by tetanus toxin or by the deletion of munc13, inhibits the activity-dependent redistribution of synapsin from the pre-synaptic terminal into the axon...
  29. Yang Y, Calakos N. Munc13-1 is required for presynaptic long-term potentiation. J Neurosci. 2011;31:12053-7 pubmed publisher
    ..b>Munc13 proteins are active zone proteins that are essential for synaptic vesicle priming and neurotransmitter release...
  30. 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
    ..To address this question, genetic mouse models with compromised glutamate release [Munc13-1-knockout (KO) and Munc13-1/2 double-KO (DKO)] and chronic pharmacological treatments interfering with specific ..
  31. Jenny Zhou H, Qin L, Zhang H, Tang W, Ji W, He Y, et al. Endothelial exocytosis of angiopoietin-2 resulting from CCM3 deficiency contributes to cerebral cavernous malformation. Nat Med. 2016;22:1033-1042 pubmed publisher
    ..in investigating the role of endothelial cell exocytosis in CCM disease progression, we found that CCM3 suppresses UNC13B- and vesicle-associated membrane protein 3 (VAMP3)-dependent exocytosis of angiopoietin 2 (ANGPT2) in brain ..
  32. Fukuda M. Alternative splicing in the first alpha-helical region of the Rab-binding domain of Rim regulates Rab3A binding activity: is Rim a Rab3 effector protein during evolution?. Genes Cells. 2004;9:831-42 pubmed
    ..Based on these findings, I propose that the Rab3A-effector function of Rim during secretory vesicle exocytosis is limited to the short form of the mammalian Rim RBD alone. ..
  33. 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
    ..In hippocampal neurons, two different Munc13s-Munc13-1 and bMunc13-2-mediate opposite forms of presynaptic short-term plasticity and thus differentially affect ..
  34. 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
    b>Munc13 catalyzes the transit of syntaxin from a closed complex with Munc18 into the ternary SNARE complex...
  35. 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...
  36. Cooper B, Hemmerlein M, Ammermüller J, Imig C, Reim K, Lipstein N, et al. Munc13-independent vesicle priming at mouse photoreceptor ribbon synapses. J Neurosci. 2012;32:8040-52 pubmed publisher
    b>Munc13 proteins are essential regulators of exocytosis...
  37. Walter A, Müller R, Tawfik B, Wierda K, Pinheiro P, Nadler A, et al. Phosphatidylinositol 4,5-bisphosphate optical uncaging potentiates exocytosis. elife. 2017;6: pubmed publisher
    ..uncaging potentiates exocytosis and identify synaptotagmin-1 (the Ca2+ sensor for exocytosis) and Munc13-2 (a vesicle priming protein) as the relevant effector proteins...