Munc-18

Munc-18 (an acronym for mammalian uncoordinated-18) protein is the mammalian homologue of the unc-18 protein (which can be found in organisms such as the C. elegans) and is a member of the Sec1/Munc18-like (SM) protein family. Munc-18 has been identified as an essential component of the synaptic vesicle fusion protein complex and crucial for the regulated exocytosis of neurons and neuroendocrine cells.^[1]

Function

Munc-18 binds syntaxin and forms a syntaxin/munc-18 complex which is thought to precede and/or regulate the formation of vesicle priming, a process mediated by VAMP, SNAP-25 and syntaxin.^[2] Munc18-1, a member of the SM family, has multiple roles in exocytosis ^[3]. It directly promotes syntaxin stability and either controls the spatially correct assembly of core complexes for SNARE-dependent fusion, or acts as a direct component of the fusion machinery through the interaction with SNARE core.^[4] Deletion of munc18-1 leads to a defect in secretory vesicle docking.^[5] Furthermore, the munc18-1 deficient mouse is the first mouse model wherein neurotransmitter secretion is completely absent. This mouse model is appropriately titled the "silent mouse."^[6]

Family members

The following is a list of human munc-18 proteins:

protein	gene
	symbol	name
MUNC18-1	STXBP1	syntaxin binding protein 1
MUNC18-2	STXBP2	syntaxin binding protein 2
MUNC18-3	STXBP3	syntaxin binding protein 3
MUNC18-4	STXBP4	syntaxin binding protein 4
MUNC18-5	STXBP5	syntaxin binding protein 5
MUNC18-6	STXBP6	syntaxin binding protein 6

See also

• Vesicle fusion
• Exocytosis
• Syntaxin
• SNARE

References

1. ^ Zilly FE, Sørensen JB, Jahn R, Lang T (October 2006). "Munc18-bound syntaxin readily forms SNARE complexes with synaptobrevin in native plasma membranes". PLoS Biol. 4 (10): e330. doi:10.1371/journal.pbio.0040330. PMC 1570500. PMID 17002520. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1570500. 
2. ^ Pevsner J, Hsu SC, Braun JE, Calakos N, Ting AE, Bennett MK, Scheller RH (August 1994). "Specificity and regulation of a synaptic vesicle docking complex". Neuron 13 (2): 353–61. doi:10.1016/0896-6273(94)90352-2. PMID 8060616. 
3. ^ Burgoyne RD, Barclay JW, Ciufo LF, Graham ME, Handley MT, Morgan A. (2009). "The functions of Munc18-1 in regulated exocytosis.". Ann N Y Acad Sci 1152: 76–86. PMID 19161378. 
4. ^ Diao J, Su Z, Lu X, Yoon TY, Shin YK, Ha T (March 2010). "Single-Vesicle Fusion Assay Reveals Munc18-1 Binding to the SNARE Core Is Sufficient for Stimulating Membrane Fusion.". ACS Chem Neurosci 1 (3): 168–174. doi:10.1021/cn900034p. PMID 20300453. 
5. ^ Toonen RF, de Vries KJ, Zalm R, Südhof TC, Verhage M (June 2005). "Munc18-1 stabilizes syntaxin 1, but is not essential for syntaxin 1 targeting and SNARE complex formation". J. Neurochem. 93 (6): 1393–400. doi:10.1111/j.1471-4159.2005.03128.x. PMID 15935055. 
6. ^ http://www.eni-net.org/organization/members/prof-matthijs-verhage/

External links

• MeSH Munc18+Proteins