7t81

Structural highlights

Function

UN13A_RAT Plays a role in vesicle maturation during exocytosis as a target of the diacylglycerol second messenger pathway. Involved in neurotransmitter release by acting in synaptic vesicle priming prior to vesicle fusion and participates in the activity-dependent refilling of readily releasable vesicle pool (RRP). Essential for synaptic vesicle maturation in most excitatory/glutamatergic but not inhibitory/GABA-mediated synapses. Also involved in secretory granule priming in insulin secretion.^{[1] [2] [3]} UN13A_MOUSE Plays a role in vesicle maturation during exocytosis as a target of the diacylglycerol second messenger pathway. Involved in neurotransmitter release by acting in synaptic vesicle priming prior to vesicle fusion and participates in the activity-dependent refilling of readily releasable vesicle pool (RRP). Essential for synaptic vesicle maturation in most excitatory/glutamatergic but not inhibitory/GABA-mediated synapses. Facilitates neuronal dense core vesicles fusion as well as controls the location and efficiency of their synaptic release (PubMed:23229896). Also involved in secretory granule priming in insulin secretion. Plays a role in dendrite formation by melanocytes (By similarity).[UniProtKB:Q62768][UniProtKB:Q9UPW8]^{[4] [5] [6] [7] [8] [9] [10] [11]}

References

1. ↑ Betz A, Ashery U, Rickmann M, Augustin I, Neher E, Sudhof TC, Rettig J, Brose N. Munc13-1 is a presynaptic phorbol ester receptor that enhances neurotransmitter release. Neuron. 1998 Jul;21(1):123-36. PMID:9697857
2. ↑ Betz A, Thakur P, Junge HJ, Ashery U, Rhee JS, Scheuss V, Rosenmund C, Rettig J, Brose N. Functional interaction of the active zone proteins Munc13-1 and RIM1 in synaptic vesicle priming. Neuron. 2001 Apr;30(1):183-96. PMID:11343654
3. ↑ Rhee JS, Betz A, Pyott S, Reim K, Varoqueaux F, Augustin I, Hesse D, Sudhof TC, Takahashi M, Rosenmund C, Brose N. Beta phorbol ester- and diacylglycerol-induced augmentation of transmitter release is mediated by Munc13s and not by PKCs. Cell. 2002 Jan 11;108(1):121-33. PMID:11792326
4. ↑ Augustin I, Rosenmund C, Sudhof TC, Brose N. Munc13-1 is essential for fusion competence of glutamatergic synaptic vesicles. Nature. 1999 Jul 29;400(6743):457-61. doi: 10.1038/22768. PMID:10440375 doi:http://dx.doi.org/10.1038/22768
5. ↑ Varoqueaux F, Sigler A, Rhee JS, Brose N, Enk C, Reim K, Rosenmund C. 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 Jun 25;99(13):9037-42. doi:, 10.1073/pnas.122623799. Epub 2002 Jun 17. PMID:12070347 doi:http://dx.doi.org/10.1073/pnas.122623799
6. ↑ Varoqueaux F, Sons MS, Plomp JJ, Brose N. Aberrant morphology and residual transmitter release at the Munc13-deficient mouse neuromuscular synapse. Mol Cell Biol. 2005 Jul;25(14):5973-84. doi: 10.1128/MCB.25.14.5973-5984.2005. PMID:15988013 doi:http://dx.doi.org/10.1128/MCB.25.14.5973-5984.2005
7. ↑ Kwan EP, Xie L, Sheu L, Nolan CJ, Prentki M, Betz A, Brose N, Gaisano HY. Munc13-1 deficiency reduces insulin secretion and causes abnormal glucose tolerance. Diabetes. 2006 May;55(5):1421-9. doi: 10.2337/db05-1263. PMID:16644700 doi:http://dx.doi.org/10.2337/db05-1263
8. ↑ Kang L, He Z, Xu P, Fan J, Betz A, Brose N, Xu T. Munc13-1 is required for the sustained release of insulin from pancreatic beta cells. Cell Metab. 2006 Jun;3(6):463-8. Epub 2006 May 11. PMID:16697276 doi:http://dx.doi.org/S1550-4131(06)00152-5
9. ↑ Basu J, Betz A, Brose N, Rosenmund C. Munc13-1 C1 domain activation lowers the energy barrier for synaptic vesicle fusion. J Neurosci. 2007 Jan 31;27(5):1200-10. doi: 10.1523/JNEUROSCI.4908-06.2007. PMID:17267576 doi:http://dx.doi.org/10.1523/JNEUROSCI.4908-06.2007
10. ↑ Kwan EP, Xie L, Sheu L, Ohtsuka T, Gaisano HY. 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 Oct;56(10):2579-88. Epub 2007 Jul 16. PMID:17639022 doi:http://dx.doi.org/db06-1207
11. ↑ van de Bospoort R, Farina M, Schmitz SK, de Jong A, de Wit H, Verhage M, Toonen RF. Munc13 controls the location and efficiency of dense-core vesicle release in neurons. J Cell Biol. 2012 Dec 10;199(6):883-91. doi: 10.1083/jcb.201208024. PMID:23229896 doi:http://dx.doi.org/10.1083/jcb.201208024