UNC13B

Summary

Gene Symbol: UNC13B
Description: unc-13 homolog B
Alias: MUNC13, UNC13, Unc13h2, protein unc-13 homolog B, homolog of rat Munc13 (diacylglycerol-binding), munc13-2, unc-13-like
Species: human
Products:     UNC13B

Top Publications

  1. Betz A, Okamoto M, Benseler F, Brose N. Direct interaction of the rat unc-13 homologue Munc13-1 with the N terminus of syntaxin. J Biol Chem. 1997;272:2520-6 pubmed
    ..b>Munc13-1 is one of three closely related rat homologues of unc-13...
  2. Orita S, Naito A, Sakaguchi G, Maeda M, Igarashi H, Sasaki T, et al. Physical and functional interactions of Doc2 and Munc13 in Ca2+-dependent exocytotic machinery. J Biol Chem. 1997;272:16081-4 pubmed
    Doc2 has two C2 domains that interact with Ca2+ and phospholipid. Munc13 has two C2 domains and one C1 domain that interacts with phorbol ester or diacylglycerol (DAG) and phospholipid...
  3. Song Y, Ailenberg M, Silverman M. Cloning of a novel gene in the human kidney homologous to rat munc13s: its potential role in diabetic nephropathy. Kidney Int. 1998;53:1689-95 pubmed
    ..This strategy resulted in cloning of a novel gene in human MC, human munc13 (hmunc13), a human homologue of rat munc13s with the N-terminal segment similar to munc13-1 and the C-terminal ..
  4. Song Y, Ailenberg M, Silverman M. Human munc13 is a diacylglycerol receptor that induces apoptosis and may contribute to renal cell injury in hyperglycemia. Mol Biol Cell. 1999;10:1609-19 pubmed
    We have previously shown that human munc13 (hmunc13) is up-regulated by hyperglycemia under in vitro conditions in human mesangial cell cultures. The purpose of the present study was to determine the cellular function of hmunc13...
  5. 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
    b>Munc13-1 and DOC2 have been implicated in the regulation of exocytosis...
  6. Schoch S, Castillo P, Jo T, Mukherjee K, Geppert M, Wang Y, et al. RIM1alpha forms a protein scaffold for regulating neurotransmitter release at the active zone. Nature. 2002;415:321-6 pubmed
    ..putative effector for the synaptic vesicle protein Rab3A, interacts with several active zone molecules, including Munc13-1 (ref. 6) and alpha-liprins, to form a protein scaffold in the presynaptic nerve terminal...
  7. Betz A, Thakur P, Junge H, Ashery U, Rhee J, Scheuss V, et al. Functional interaction of the active zone proteins Munc13-1 and RIM1 in synaptic vesicle priming. Neuron. 2001;30:183-96 pubmed
    ..We show that the active zone components Munc13-1, an essential vesicle priming protein, and RIM1, a Rab3 effector with a putative role in vesicle tethering, ..
  8. Karkhanis A, Leach A, Yorgason J, Uneri A, Barth S, Niere F, et al. Chronic Social Isolation Stress during Peri-Adolescence Alters Presynaptic Dopamine Terminal Dynamics via Augmentation in Accumbal Dopamine Availability. ACS Chem Neurosci. 2019;10:2033-2044 pubmed publisher
    ..Western blot analysis of release machinery proteins (VMAT2, Synaptogyrin-3, Syntaxin-1, and Munc13-3) showed no difference between the two groups...
  9. Sepulveda F, Burgess A, Heiligenstein X, Goudin N, Ménager M, Romao M, et al. LYST controls the biogenesis of the endosomal compartment required for secretory lysosome function. Traffic. 2015;16:191-203 pubmed publisher
    ..By increasing the expression of effectors of lytic granule exocytosis, such as Munc13-4, Rab27a and Slp3, in CHS CTLs, we were able to restore the dynamics and the secretory ability of cytotoxic ..

More Information

Publications133 found, 100 shown here

  1. 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
    ..Strikingly, CaM inhibitors or the inhibition of the Ca(2+)-calmodulin-Munc13-1 signaling pathway only impaired the uptake of Syt2 while leaving membrane retrieval intact, indicating different ..
  2. Ferrante L, Rognum T, Vege Ã, NygÃ¥rd S, Opdal S. Altered gene expression and possible immunodeficiency in cases of sudden infant death syndrome. Pediatr Res. 2016;80:77-84 pubmed publisher
    ..downregulation of MyD88 in tissue from SIDS brains, as well as the downregulation of the genes encoding CCL3 and UNC13 in the liver...
  3. Gioia D, MCCOOL B. Strain-Dependent Effects of Acute Alcohol on Synaptic Vesicle Recycling and Post-Tetanic Potentiation in Medial Glutamate Inputs to the Mouse Basolateral Amygdala. Alcohol Clin Exp Res. 2017;41:735-746 pubmed publisher
    ..to synaptic vesicle priming in addition to PTP have been implicated in alcohol-related behaviors, including Munc13, Munc18, and RIM proteins, making them potential candidates for the molecular mechanism controlling these effects.
  4. Petrie M, Esquibel J, Kabachinski G, Maciuba S, Takahashi H, Edwardson J, et al. The Vesicle Priming Factor CAPS Functions as a Homodimer via C2 Domain Interactions to Promote Regulated Vesicle Exocytosis. J Biol Chem. 2016;291:21257-21270 pubmed
    ..Comparison of the CAPS C2 domain to a structurally defined Munc13-1 C2A domain dimer revealed conserved residues involved in CAPS dimerization...
  5. Kurz A, Pruenster M, Rohwedder I, Ramadass M, Schäfer K, Harrison U, et al. MST1-dependent vesicle trafficking regulates neutrophil transmigration through the vascular basement membrane. J Clin Invest. 2016;126:4125-4139 pubmed publisher
    ..associates with the Rab27 effector protein synaptotagmin-like protein 1 (JFC1, encoded by Sytl1 in mice), but not Munc13-4, thereby regulating the trafficking of Rab27-positive vesicles to the cellular membrane...
  6. Marengo F, Cárdenas A. How does the stimulus define exocytosis in adrenal chromaffin cells?. Pflugers Arch. 2018;470:155-167 pubmed publisher
    ..N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins, Ca2+ sensors like Munc13 and synaptotagmin-1, chaperon proteins such as Munc18, and the actomyosin complex...
  7. Ferrero J, Ramírez Franco J, Martín R, Bartolomé Martín D, Torres M, Sánchez Prieto J. Cross-talk between metabotropic glutamate receptor 7 and beta adrenergic receptor signaling at cerebrocortical nerve terminals. Neuropharmacology. 2016;101:412-25 pubmed publisher
    ..receptors also enhances PLC-dependent accumulation of IP1 and the translocation of the active zone protein Munc13-1 to the membrane, indicating that release potentiation by these receptors involves the modulation of the release ..
  8. Candiello E, Mishra R, Schmidt B, Jahn O, Schu P. Differential regulation of synaptic AP-2/clathrin vesicle uncoating in synaptic plasticity. Sci Rep. 2017;7:15781 pubmed publisher
    ..Endocytosis of the synaptic vesicle exocytosis regulating Munc13 isoforms are differentially effected...
  9. Sarath Babu N, Murthy C, Kakara S, Sharma R, Brahmendra Swamy C, Idris M. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine induced Parkinson's disease in zebrafish. Proteomics. 2016;16:1407-20 pubmed publisher
    ..Proteins such as NEFL, MUNC13-1, NAV2 and GAPVD1 were down regulated in the zebrafish brain for the PD phenotype, which were associated with the ..
  10. Popko K, Jasinska J, Gorska E, Demkow U, Balwierz W, Maciejka Kembłowska L, et al. Impairment of Immune Function in Children with Familial Hemophagocytic Lymphohistiocytosis. Adv Exp Med Biol. 2016;912:21-31 pubmed publisher
    ..09). In case of patients with mutation in the Munc13 protein, degranulation was lower than that in healthy children (<5 %)...
  11. Zhao S, Mugabo Y, Iglesias J, Xie L, Delghingaro Augusto V, Lussier R, et al. α/β-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...
  12. Kamoun F, Hsairi M, Grandin V, Ben Ameur S, de Saint Basile G, Hachicha M. Familial haemophagocytosis lymphohisticytosis type 3: A case report. Arch Pediatr. 2017;24:33-35 pubmed publisher
    ..The diagnosis of FHL type 3 was made by the identification of homozygous mutation in the Munc13-4 gene (UNC13D) located in exon 20: 1822 del 12bp (V608fs)...
  13. Lorenzoni P, Scola R, Kay C, Werneck L, Horvath R, Lochmuller H. How to Spot Congenital Myasthenic Syndromes Resembling the Lambert-Eaton Myasthenic Syndrome? A Brief Review of Clinical, Electrophysiological, and Genetics Features. Neuromolecular Med. 2018;20:205-214 pubmed publisher
    ..To date, the genes that have been associated with CMS-LEMS are AGRN, SYT2, MUNC13-1, VAMP1, and LAMA5...
  14. Quesnel Vallières M, Irimia M, Cordes S, Blencowe B. Essential roles for the splicing regulator nSR100/SRRM4 during nervous system development. Genes Dev. 2015;29:746-59 pubmed publisher
    ..Remarkably, inclusion of a 6-nt, nSR100-activated microexon in Unc13b transcripts is sufficient to rescue a neuritogenesis defect in nSR100 mutant primary neurons...
  15. Engel A. Congenital Myasthenic Syndromes in 2018. Curr Neurol Neurosci Rep. 2018;18:46 pubmed publisher
    ..The identified disease proteins are SNAP25B, synaptotagmin 2, Munc13-1, synaptobrevin-1, GFPT1, DPAGT1, ALG2, ALG14, Agrin, GMPPB, LRP4, myosin 9A, collagen 13A1, the mitochondrial ..
  16. Brunger A, Choi U, Lai Y, Leitz J, Zhou Q. Molecular Mechanisms of Fast Neurotransmitter Release. Annu Rev Biophys. 2018;47:469-497 pubmed publisher
    ..sensitive factor attachment protein receptors), synaptotagmin, complexin, Munc18 (mammalian uncoordinated-18), and Munc13 (mammalian uncoordinated-13), and highlights recent insights in the cooperation of these proteins for ..
  17. 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...
  18. Nguyen Truong C, Nestvogel D, Ratai O, Schirra C, Stevens D, Brose N, et al. Secretory vesicle priming by CAPS is independent of its SNARE-binding MUN domain. Cell Rep. 2014;9:902-9 pubmed publisher
    ..This process apparently requires membrane phospholipids, does not involve the binding or direct conformational regulation of syntaxin by MUN domains of CAPSs, and is therefore not redundant with Munc13 action.
  19. Rothman J, Krishnakumar S, Grushin K, Pincet F. Hypothesis - buttressed rings assemble, clamp, and release SNAREpins for synaptic transmission. FEBS Lett. 2017;591:3459-3480 pubmed publisher
    ..We suggest that an outer ring of up to six curved Munc13 'MUN' domains transiently anchored to the plasma membrane via its flanking domains surrounds a stable inner ring ..
  20. Brunger A, Leitz J, Zhou Q, Choi U, Lai Y. Ca2+-Triggered Synaptic Vesicle Fusion Initiated by Release of Inhibition. Trends Cell Biol. 2018;28:631-645 pubmed publisher
    ..to extended synaptotagmin C2 domains enables lipid transport by releasing an inhibited state of the system, and that Munc13 may nominally be in an inhibited state, which is released upon Ca2+ binding to one of its C2 domains.
  21. Brunger A, Choi U, Lai Y, Leitz J, White K, Zhou Q. The pre-synaptic fusion machinery. Curr Opin Struct Biol. 2019;54:179-188 pubmed publisher
    ..Functional studies have revealed roles of the essential factors Munc18 and Munc13, demonstrating that a part of their function involves the proper assembly of synaptic protein complexes...
  22. Cardenas E, Breaux K, Da Q, Flores J, Ramos M, Tuvim M, et al. Platelet Munc13-4 regulates hemostasis, thrombosis and airway inflammation. Haematologica. 2018;103:1235-1244 pubmed publisher
    ..Exocytosis in platelets is mediated by SNARE proteins and should be controlled by Munc13 proteins. We found that platelets express Munc13-2 and -4...
  23. Yuan Q, Zhou J, Teng L, Liu C, Guo J, Liu L, et al. Intrauterine growth retardation leads to the functional change of insulin secretion in the newborn rats. Horm Metab Res. 2010;42:491-5 pubmed publisher
    ..were observed in mRNA level of insulin and PDX-1, the expression of genes related to insulin exocytosis such as munc13-1, vamp-2, syntaxin1a, rab3a were reduced significantly in IUGR newborn rats. IUGR animals were glucose-intolerant...
  24. Netrakanti P, Cooper B, Dere E, Poggi G, Winkler D, Brose N, et al. Fast cerebellar reflex circuitry requires synaptic vesicle priming by munc13-3. Cerebellum. 2015;14:264-83 pubmed publisher
    b>Munc13-3 is a member of the Munc13 family of synaptic vesicle priming proteins and mainly expressed in cerebellar neurons...
  25. de Jong A, Meijer M, Saarloos I, Cornelisse L, Toonen R, Sørensen J, et al. Phosphorylation of synaptotagmin-1 controls a post-priming step in PKC-dependent presynaptic plasticity. Proc Natl Acad Sci U S A. 2016;113:5095-100 pubmed publisher
    ..Two substrates, Munc13-1 and Munc18-1, are essential for DAG-induced potentiation of vesicle priming, but the role of most presynaptic ..
  26. Hsieh M, Ho Y, Lai C, Chou D, Chen G, Lin T, et al. Spinal TNF-? impedes Fbxo45-dependent Munc13-1 ubiquitination to mediate neuropathic allodynia in rats. Cell Death Dis. 2018;9:811 pubmed publisher
    ..allodynia, neuropathic injury induced a marked elevation in the expression levels of an active zone protein Munc13-1 in the homogenate and synaptic plasma membrane of the ipsilateral dorsal horn...
  27. Huang C, Chiu T, Lee T, Hsieh H, Lin C, Kao L. Soluble α-synuclein facilitates priming and fusion by releasing Ca2+ from the thapsigargin-sensitive Ca2+ pool in PC12 cells. J Cell Sci. 2018;131: pubmed publisher
    ..and explored the molecular mechanism by which α-synuclein interacts with regulatory proteins, including Rab3A, Munc13-1 (also known as Unc13a) and Munc18-1 (also known as STXBP1), in order to regulate exocytosis...
  28. Wang S, Li Y, Gong J, Ye S, Yang X, Zhang R, et al. Munc18 and Munc13 serve as a functional template to orchestrate neuronal SNARE complex assembly. Nat Commun. 2019;10:69 pubmed publisher
    ..of the Munc18-1/syntaxin-1 complex to the SNARE complex, a key step involved in exocytosis, is regulated by Munc13-1, SNAP-25 and synaptobrevin-2, but the underlying mechanism remains elusive...
  29. Hiejima E, Shibata H, Yasumi T, Shimodera S, Hori M, Izawa K, et al. Characterization of a large UNC13D gene duplication in a patient with familial hemophagocytic lymphohistiocytosis type 3. Clin Immunol. 2018;191:63-66 pubmed publisher
    ..type 3 is a life-threatening immune dysregulation syndrome caused by mutations in the UNC13D gene, encoding the munc13-4 protein, which is important for function of cytotoxic lymphocytes...
  30. Ishiyama S, Schmidt H, Cooper B, Brose N, Eilers J. Munc13-3 superprimes synaptic vesicles at granule cell-to-basket cell synapses in the mouse cerebellum. J Neurosci. 2014;34:14687-96 pubmed publisher
    b>Munc13-3 is a presynaptic protein implicated in vesicle priming that is strongly expressed in cerebellar granule cells (GCs)...
  31. 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...
  32. Bell C, Teschendorff A, Rakyan V, Maxwell A, Beck S, Savage D. Genome-wide DNA methylation analysis for diabetic nephropathy in type 1 diabetes mellitus. BMC Med Genomics. 2010;3:33 pubmed publisher
    ..Of note, this included one CpG site located 18 bp upstream of the transcription start site of UNC13B, a gene in which the first intronic SNP rs13293564 has recently been reported to be associated with diabetic ..
  33. Xu R, Zhou J, Zhou X, Li Q, Perelman J, Kolosov V. Munc13‑4 mediates human neutrophil elastase‑induced airway mucin5AC hypersecretion by interacting with syntaxin2. Mol Med Rep. 2018;18:1015-1024 pubmed publisher
    ..Mucin5AC (MUC5AC) is a major component of airway gel‑forming mucin. Members of the Unc13 (Munc13) protein family act as important activators of granule exocytosis from various types of mammalian cells...
  34. Crescente M, Pluthero F, Li L, Lo R, Walsh T, Schenk M, et al. Intracellular Trafficking, Localization, and Mobilization of Platelet-Borne Thiol Isomerases. Arterioscler Thromb Vasc Biol. 2016;36:1164-73 pubmed publisher
    ..of actin polymerization (inhibited by latrunculin) and in the presence or absence of membrane fusion mediated by Munc13-4 (absent in platelets from Unc13d(Jinx) mice)...
  35. 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...
  36. Han Y, Babai N, Kaeser P, Südhof T, Schneggenburger R. RIM1 and RIM2 redundantly determine Ca2+ channel density and readily releasable pool size at a large hindbrain synapse. J Neurophysiol. 2015;113:255-63 pubmed publisher
    ..The long isoforms of RIM proteins, which contain NH2-terminal Rab3- and Munc13-interacting domains, as well as a central PDZ domain and two COOH-terminal C2 domains, are encoded by two genes, ..
  37. Holt O, Kanno E, Bossi G, Booth S, Daniele T, Santoro A, et al. Slp1 and Slp2-a localize to the plasma membrane of CTL and contribute to secretion from the immunological synapse. Traffic. 2008;9:446-57 pubmed publisher
    ..A series of Rab27a-interacting proteins have been identified; however, only Munc13-4 has been found to be expressed in CTL...
  38. Zhang X, Jiang S, Mitok K, Li L, Attie A, Martin T. BAIAP3, a C2 domain-containing Munc13 protein, controls the fate of dense-core vesicles in neuroendocrine cells. J Cell Biol. 2017;216:2151-2166 pubmed publisher
    ..including several encoding proteins with known roles (CAPS [calcium-dependent activator protein for secretion 1], Munc13-2, RIM1, and SYT10) and many with unknown roles...
  39. 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 ..
  40. Yang X, Wang S, Sheng Y, Zhang M, Zou W, Wu L, et al. Syntaxin opening by the MUN domain underlies the function of Munc13 in synaptic-vesicle priming. Nat Struct Mol Biol. 2015;22:547-54 pubmed publisher
    ..The crystal structure of the rat Munc13-1 MUN domain now reveals an elongated, arch-shaped architecture formed by α-helical bundles, with a highly ..
  41. Johnson J, He J, Ramadass M, Pestonjamasp K, Kiosses W, Zhang J, et al. Munc13-4 Is a Rab11-binding Protein That Regulates Rab11-positive Vesicle Trafficking and Docking at the Plasma Membrane. J Biol Chem. 2016;291:3423-38 pubmed publisher
    ..b>Munc13-4 is a docking factor proposed to regulate fusion through interactions with SNAREs...
  42. Yang F, Dong A, Ahamed J, Sunkara M, Smyth S. Granule cargo release from bone marrow-derived cells sustains cardiac hypertrophy. Am J Physiol Heart Circ Physiol. 2014;307:H1529-38 pubmed publisher
    ..One potential mechanism is through release of granule cargo. Unc13-d(Jinx) (Jinx) mice, which lack Munc13-4, a limiting factor in vesicular priming and fusion, have granule secretion defects in a variety of hematopoietic ..
  43. Fan F, Matsunaga K, Wang H, Ishizaki R, Kobayashi E, Kiyonari H, et al. Exophilin-8 assembles secretory granules for exocytosis in the actin cortex via interaction with RIM-BP2 and myosin-VIIa. elife. 2017;6: pubmed publisher
    ..RIM-BP2 also associates with exocytic machinery, Cav1.3, RIM, and Munc13-1...
  44. Franciszkiewicz K, Boutet M, Gauthier L, Vergnon I, Peeters K, Duc O, et al. Synaptic release of CCL5 storage vesicles triggers CXCR4 surface expression promoting CTL migration in response to CXCL12. J Immunol. 2014;193:4952-61 pubmed publisher
    ..We propose that CCL5 polarized delivery represents a mechanism by which CTL control immune synapse duration. ..
  45. Sørensen J. Ride the wave: Retrograde trafficking becomes Ca2+ dependent with BAIAP3. J Cell Biol. 2017;216:1887-1889 pubmed publisher
    The functions of four of the five proteins in the mammalian uncoordinated-13 (Munc13) family have been identified as priming factors in SNARE-dependent exocytosis. In this issue, Zhang et al. (2017. J. Cell Biol. https://doi.org/10...
  46. Bin N, Ma K, Tien C, Wang S, Zhu D, Park S, et al. C2 Domains of Munc13-4 Are Crucial for Ca2+-Dependent Degranulation and Cytotoxicity in NK Cells. J Immunol. 2018;201:700-713 pubmed publisher
    ..we show multiple lines of evidence in which point mutations in aspartic acid residues in both C2 domains of human Munc13-4, whose mutation underlies familial hemophagocytic lymphohistiocytosis type 3, diminished exocytosis with ..
  47. Liu X, Seven A, Camacho M, Esser V, Xu J, Trimbuch T, et al. Functional synergy between the Munc13 C-terminal C1 and C2 domains. elife. 2016;5: pubmed publisher
    ..and electrophysiological experiments now reveal a functional synergy between the C1, C2B and C2C domains of Munc13-1, indicating that these domains help bridging the vesicle and plasma membranes to facilitate stimulation of SNARE ..
  48. Bordbar M, Modarresi F, Farazi Fard M, Dastsooz H, Shakib Azad N, Faghihi M. A case report of novel mutation in PRF1 gene, which causes familial autosomal recessive hemophagocytic lymphohistiocytosis. BMC Med Genet. 2017;18:49 pubmed publisher
    ..genes involved in these steps play important roles in the pathogenesis of HLH disease which include PRF1, UNC13D (MUNC13-4), STX11, and STXBP2 (MUNC18-2)...
  49. 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...
  50. Wojcik S, Tantra M, Stepniak B, Man K, Müller Ribbe K, Begemann M, et al. Genetic markers of a Munc13 protein family member, BAIAP3, are gender specifically associated with anxiety and benzodiazepine abuse in mice and humans. Mol Med. 2013;19:135-48 pubmed publisher
    ..angiogenesis inhibitor I-associated protein 3 (Baiap3) is a member of the mammalian uncoordinated 13 (Munc13) protein family of synaptic regulators of neurotransmitter exocytosis, with a striking expression pattern in ..
  51. Yamaga M, Kielar Grevstad D, Martin T. Phospholipase Cη2 Activation Redirects Vesicle Trafficking by Regulating F-actin. J Biol Chem. 2015;290:29010-21 pubmed publisher
    ..by regulating the activities of the lipid-dependent priming factors CAPS (also known as CADPS) and ubiquitous Munc13-2 in PC12 cells...
  52. Woo S, James D, Martin T. Munc13-4 functions as a Ca2+ sensor for homotypic secretory granule fusion to generate endosomal exocytic vacuoles. Mol Biol Cell. 2017;28:792-808 pubmed publisher
    b>Munc13-4 is a Ca2+-dependent SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor)- and phospholipid-binding protein that localizes to and primes secretory granules (SGs) for Ca2+-..
  53. Poursharifi P, Madiraju S, Prentki M. Monoacylglycerol signalling and ABHD6 in health and disease. Diabetes Obes Metab. 2017;19 Suppl 1:76-89 pubmed publisher
    ..Diverse cellular targets such as mammalian unc13-1 (Munc13-1), PPARs, GPR119 and CB1/2 receptors, for MAG-mediated signalling processes have been proposed in different cell ..
  54. Boswell K, James D, Esquibel J, Bruinsma S, Shirakawa R, Horiuchi H, et al. Munc13-4 reconstitutes calcium-dependent SNARE-mediated membrane fusion. J Cell Biol. 2012;197:301-12 pubmed publisher
    b>Munc13-4 is a widely expressed member of the CAPS/Munc13 protein family proposed to function in priming secretory granules for exocytosis...
  55. 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 ..
  56. Jonnalagadda D, Sunkara M, Morris A, Whiteheart S. Granule-mediated release of sphingosine-1-phosphate by activated platelets. Biochim Biophys Acta. 2014;1841:1581-9 pubmed publisher
    ..g. platelet factor IV (PF4). Agonist-stimulated S1P release was defective in platelets from Unc13d(Jinx) (Munc13-4 null) mice demonstrating a critical role for regulated membrane fusion in this process...
  57. Chehab T, Santos N, Holthenrich A, Koerdt S, Disse J, Schuberth C, et al. A novel Munc13-4/S100A10/annexin A2 complex promotes Weibel-Palade body exocytosis in endothelial cells. Mol Biol Cell. 2017;28:1688-1700 pubmed publisher
    ..Here we identify Munc13-4, a protein mutated in familial hemophagocytic lymphohistiocytosis 3, as a WPB-tethering factor...
  58. 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 ..
  59. Messenger S, Woo S, Sun Z, Martin T. A Ca2+-stimulated exosome release pathway in cancer cells is regulated by Munc13-4. J Cell Biol. 2018;217:2877-2890 pubmed publisher
    ..b>Munc13-4 is a Ca2+-dependent SNAP receptor- and Rab-binding protein required for Ca2+-dependent ..
  60. Xue R, Ruhl D, Briguglio J, Figueroa A, Pearce R, Chapman E. Doc2-mediated superpriming supports synaptic augmentation. Proc Natl Acad Sci U S A. 2018;115:E5605-E5613 pubmed publisher
    ..Doc2 binds Ca2+ and munc13 and translocates to the plasma membrane to drive augmentation...
  61. Krzewski K, Cullinane A. Evidence for defective Rab GTPase-dependent cargo traffic in immune disorders. Exp Cell Res. 2013;319:2360-7 pubmed publisher
    ..In lymphocytes, Munc13-4 is an effector of Rab27a, and mutations in the gene encoding this protein (UNC13D) cause Familial Hemophagocytic ..
  62. Cetica V, Hackmann Y, Grieve S, Sieni E, Ciambotti B, Coniglio M, et al. Patients with Griscelli syndrome and normal pigmentation identify RAB27A mutations that selectively disrupt MUNC13-4 binding. J Allergy Clin Immunol. 2015;135:1310-8.e1 pubmed publisher
    ..carried mutations at amino acids R141, Y159, or S163 of Rab27a that disrupt the interaction of Rab27a with Munc13-4, without impairing the interaction between melanophilin and Rab27a...
  63. Bruinsma S, James D, Quintana Serrano M, Esquibel J, Woo S, Kielar Grevstad E, et al. Small molecules that inhibit the late stage of Munc13-4-dependent secretory granule exocytosis in mast cells. J Biol Chem. 2018;293:8217-8229 pubmed publisher
    ..machinery at late steps in the regulated secretory pathway, employing protein isoforms from the Rab, Sec1/Munc18, Munc13/CAPS, SNARE, and synaptotagmin protein families...
  64. Martin T. PI(4,5)Pâ‚‚-binding effector proteins for vesicle exocytosis. Biochim Biophys Acta. 2015;1851:785-93 pubmed publisher
    ..recruiting and activating PI(4,5)Pâ‚‚-binding proteins that regulate SNARE protein function including CAPS, Munc13-1/2, synaptotagmin-1, and other C2 domain-containing proteins...
  65. Fulterer A, Andlauer T, Ender A, Maglione M, Eyring K, Woitkuhn J, et al. Active Zone Scaffold Protein Ratios Tune Functional Diversity across Brain Synapses. Cell Rep. 2018;23:1259-1274 pubmed publisher
    ..BRP, and Syd-1) cluster-specific (M)Unc13 release factor isoforms either close (BRP/Unc13A) or further away (Syd-1/Unc13B) from VGCCs across synapses of the Drosophila olfactory system, resulting in different synapse-characteristic ..
  66. Cetica V, Santoro A, Gilmour K, Sieni E, Beutel K, Pende D, et al. STXBP2 mutations in children with familial haemophagocytic lymphohistiocytosis type 5. J Med Genet. 2010;47:595-600 pubmed publisher
    ..resulting in defective cell cytotoxicity; three disease related genes have been identified to date: perforin, Munc13-4 and syntaxin-11...
  67. Santos T, Wierda K, Broeke J, Toonen R, Verhage M. Early Golgi Abnormalities and Neurodegeneration upon Loss of Presynaptic Proteins Munc18-1, Syntaxin-1, or SNAP-25. J Neurosci. 2017;37:4525-4539 pubmed publisher
    ..syntaxin-1, Munc18-1, SNAP-25), whereas other proteins involved in the same molecular process (synaptobrevins, Munc13-1/2) do not cause degeneration...
  68. Cooke M, Zhou X, Casado Medrano V, Lopez Haber C, Baker M, Garg R, et al. Characterization of AJH-836, a diacylglycerol-lactone with selectivity for novel PKC isozymes. J Biol Chem. 2018;293:8330-8341 pubmed publisher
    ..six other families of proteins, including the chimaerins, Ras-guanyl nucleotide-releasing proteins (RasGRPs), and Munc13 isoforms, also play important roles...
  69. Iizuka Y, Cichocki F, Sieben A, Sforza F, Karim R, Coughlin K, et al. UNC-45A Is a Nonmuscle Myosin IIA Chaperone Required for NK Cell Cytotoxicity via Control of Lytic Granule Secretion. J Immunol. 2015;195:4760-70 pubmed publisher
    ..This includes Wiskott-Aldrich syndrome protein, Wiskott-Aldrich syndrome protein-interacting protein, cofilin, Munc13-4, and nonmuscle myosin IIA (NMIIA)...
  70. Sitarska E, Xu J, Park S, Liu X, Quade B, Stepien K, et al. Autoinhibition of Munc18-1 modulates synaptobrevin binding and helps to enable Munc13-dependent regulation of membrane fusion. elife. 2017;6: pubmed publisher
    Munc18-1 orchestrates SNARE complex assembly together with Munc13-1 to mediate neurotransmitter release. Munc18-1 binds to synaptobrevin, but the relevance of this interaction and its relation to Munc13 function are unclear...
  71. Torres V, Inestrosa N. Vertebrate Presynaptic Active Zone Assembly: a Role Accomplished by Diverse Molecular and Cellular Mechanisms. Mol Neurobiol. 2018;55:4513-4528 pubmed publisher
    ..At the vertebrate presynapses, proteins such as Piccolo, Bassoon, RIM, RIM-BPs, CAST/ELKS, liprin-α, and Munc13 are constant residents and participate in multiple and dynamic interactions with other regulatory proteins, which ..
  72. Wong M, Liu C, Wang S, Roquas A, Fowler S, Kaeser P. Liprin-?3 controls vesicle docking and exocytosis at the active zone of hippocampal synapses. Proc Natl Acad Sci U S A. 2018;115:2234-2239 pubmed publisher
    ..but not Liprin-?2, had a prominent component that colocalized with the active-zone proteins Bassoon, RIM, Munc13, RIM-BP, and ELKS. To assess Liprin-?3 functions, we generated Liprin-?3-KO mice by using CRISPR/Cas9 gene editing...
  73. Ohta H, Miyashita E, Hirata I, Matsumura R, Yoshida H, Hashii Y, et al. Hematopoietic stem cell transplantation with reduced intensity conditioning from a family haploidentical donor in an infant with familial hemophagocytic lymphohistocytosis. Int J Hematol. 2011;94:285-290 pubmed publisher
    ..We present a case of a 3-month-old girl with Munc13-4 mutation (FHL3), who underwent bone marrow transplantation (BMT) from her human leukocyte antigen-haploidentical ..
  74. 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 ..
  75. Böhme M, Beis C, Reddy Alla S, Reynolds E, Mampell M, Grasskamp A, et al. Active zone scaffolds differentially accumulate Unc13 isoforms to tune Ca(2+) channel-vesicle coupling. Nat Neurosci. 2016;19:1311-20 pubmed publisher
    ..and intravital imaging of developing Drosophila melanogaster glutamatergic synapses revealed that the Unc13B isoform was recruited to nascent AZs by the scaffolding proteins Syd-1 and Liprin-?, and Unc13A was positioned by ..
  76. Hori M, Yasumi T, Shimodera S, Shibata H, Hiejima E, Oda H, et al. A CD57+ CTL Degranulation Assay Effectively Identifies Familial Hemophagocytic Lymphohistiocytosis Type 3 Patients. J Clin Immunol. 2017;37:92-99 pubmed publisher
    ..were prospectively screened for FHL3 by measuring the perforin expression in NK cells and the expression of Munc13-4, syntaxin-11, and Munc18-2 in platelets and by performing NK cell and CTL degranulation assays...
  77. Wang S, Choi U, Gong J, Yang X, Li Y, Wang A, et al. Conformational change of syntaxin linker region induced by Munc13s initiates SNARE complex formation in synaptic exocytosis. EMBO J. 2017;36:816-829 pubmed publisher
    ..Although it is known that the MUN domain of Munc13-1 catalyzes the transition from the Munc18-1/syntaxin-1 complex to the SNARE complex, the molecular mechanism is ..
  78. Xu J, Camacho M, Xu Y, Esser V, Liu X, Trimbuch T, et al. Mechanistic insights into neurotransmitter release and presynaptic plasticity from the crystal structure of Munc13-1 C1C2BMUN. elife. 2017;6: pubmed publisher
    b>Munc13-1 acts as a master regulator of neurotransmitter release, mediating docking-priming of synaptic vesicles and diverse presynaptic plasticity processes...
  79. Zhang M, Bracaglia C, Prencipe G, Bemrich Stolz C, Beukelman T, Dimmitt R, et al. A Heterozygous RAB27A Mutation Associated with Delayed Cytolytic Granule Polarization and Hemophagocytic Lymphohistiocytosis. J Immunol. 2016;196:2492-503 pubmed publisher
    ..Polarization of granzyme B to the immunologic synapse and interaction of mutant Rab27A (p.A87P) with Munc13-4 were explored by confocal microscopy and proximity ligation assay, respectively...
  80. Zhao S, Poursharifi P, Mugabo Y, Levens E, Vivot K, Attane C, et al. α/β-Hydrolase domain-6 and saturated long chain monoacylglycerol regulate insulin secretion promoted by both fuel and non-fuel stimuli. Mol Metab. 2015;4:940-50 pubmed publisher
    ..lipolysis-derived MAG that acts as a metabolic coupling factor and signaling molecule via exocytotic regulator Munc13-1...
  81. Higashio H, Satoh Y, Saino T. Mast cell degranulation is negatively regulated by the Munc13-4-binding small-guanosine triphosphatase Rab37. Sci Rep. 2016;6:22539 pubmed publisher
    ..Rab27b, which have distinct and opposing roles: Rab27b acts as a positive regulator through its effector protein Munc13-4, a non-neuronal isoform of the vesicle-priming Munc13 family of proteins, whereas Rab27a acts as a negative ..
  82. Lipstein N, Göth M, Piotrowski C, Pagel K, Sinz A, Jahn O. Presynaptic Calmodulin targets: lessons from structural proteomics. Expert Rev Proteomics. 2017;14:223-242 pubmed publisher
    ..and structural proteomic methods that were used to identify and characterize the interactions between CaM and Munc13 proteins...
  83. Kabachinski G, Yamaga M, Kielar Grevstad D, Bruinsma S, Martin T. CAPS and Munc13 utilize distinct PIP2-linked mechanisms to promote vesicle exocytosis. Mol Biol Cell. 2014;25:508-21 pubmed publisher
    ..CAPS is found to reside on vesicles but depends on plasma membrane PIP2 for its activity. Munc13 is cytoplasmic, but Ca(2+)-dependent translocation to PIP2-rich plasma membrane domains is required for its ..
  84. Chicka M, Ren Q, Richards D, Hellman L, Zhang J, Fried M, et al. Role of Munc13-4 as a Ca2+-dependent tether during platelet secretion. Biochem J. 2016;473:627-39 pubmed publisher
    The Munc13 family of exocytosis regulators has multiple Ca(2+)-binding, C2 domains. Here, we probed the mechanism by which Munc13-4 regulates in vitro membrane fusion and platelet exocytosis...
  85. Kusch V, Bornschein G, Loreth D, Bank J, Jordan J, Baur D, et al. Munc13-3 Is Required for the Developmental Localization of Ca2+ Channels to Active Zones and the Nanopositioning of Cav2.1 Near Release Sensors. Cell Rep. 2018;22:1965-1973 pubmed publisher
    ..Here, we show that Munc13-3 regulates the density of Cav2.1 and Cav2...
  86. 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
    b>Munc13 proteins are essential regulators of neurotransmitter release at nerve cell synapses...
  87. He J, Johnson J, Monfregola J, Ramadass M, Pestonjamasp K, Napolitano G, et al. Munc13-4 interacts with syntaxin 7 and regulates late endosomal maturation, endosomal signaling, and TLR9-initiated cellular responses. Mol Biol Cell. 2016;27:572-87 pubmed publisher
    ..mechanism of late endosomal maturation that involves a new molecular interaction between the tethering factor Munc13-4, syntaxin 7, and VAMP8. Munc13-4 binding to syntaxin 7 was significantly increased by calcium...
  88. 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 ..
  89. Hamada S, Ohtsuka T. CAST: Its molecular structure and phosphorylation-dependent regulation of presynaptic plasticity. Neurosci Res. 2018;127:25-32 pubmed publisher
    ..active zone-specific proteins have been isolated and characterized, including Bassoon, Piccolo/Aczonin, RIM, Munc13-1, ELKS, and CAST...
  90. Löhner M, Babai N, Müller T, Gierke K, Atorf J, Joachimsthaler A, et al. Analysis of RIM Expression and Function at Mouse Photoreceptor Ribbon Synapses. J Neurosci. 2017;37:7848-7863 pubmed publisher
    ..The priming function of RIMs is mediated via the formation of a tripartite complex with Munc13 and RAB3A, which brings synaptic vesicles in close proximity to Ca2+ channels and the fusion site and ..
  91. Gandasi N, Yin P, Riz M, Chibalina M, Cortese G, Lund P, et al. Ca2+ channel clustering with insulin-containing granules is disturbed in type 2 diabetes. J Clin Invest. 2017;127:2353-2364 pubmed publisher
    ..We determined that recruitment depended on a direct interaction with the synaptic protein Munc13, because expression of the II-III loop of the channel, the C2 domain of Munc13-1, or of Munc13-1 with a mutated C2 ..
  92. Shibata H, Yasumi T, Shimodera S, Hiejima E, Izawa K, Kawai T, et al. Human CTL-based functional analysis shows the reliability of a munc13-4 protein expression assay for FHL3 diagnosis. Blood. 2018;: pubmed publisher
    ..We previously reported that FHL type 3 (FHL3) can be rapidly screened by detecting munc13-4 expression in platelets using flow cytometry; however, the reliability of the munc13-4 expression assay for FHL3 ..