Munc-18

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title: "Munc-18" type: doc version: 1 created: 2026-02-28 author: "Wikipedia contributors" status: active scope: public tags: ["neurophysiology", "human-proteins"] topic_path: "science/biology" source: "https://en.wikipedia.org/wiki/Munc-18" license: "CC BY-SA 4.0" wikipedia_page_id: 0 wikipedia_revision_id: 0

Munc-18 (an acronym for mammalian uncoordinated**-18**) proteins are the mammalian homologue of UNC-18 (which was first discovered in the nematode worm C. elegans) and are a member of the Sec1/Munc18-like (SM) protein family. Munc-18 proteins have been identified as essential components of the synaptic vesicle fusion protein complex and are crucial for the regulated exocytosis of neurons and neuroendocrine cells.

Function

Munc-18 binds syntaxin and forms a syntaxin/munc-18 complex which is thought to precede and/or regulate vesicle priming], a process mediated by VAMP, SNAP-25 and syntaxin. Munc18-1, a member of the SM family, has multiple roles in exocytosis. 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. Munc18a, which binds specifically to the N-terminal of syntaxin, causes a conformation change, activating syntaxin, which in turn connects to the ternary-SNARE complex.{{Cite journal | last1 = Kasai | first1 = H. | last2 = Takahashi | first2 = N. | last3 = Tokumaru | first3 = H. | doi = 10.1152/physrev.00007.2012 | title = Distinct Initial SNARE Configurations Underlying the Diversity of Exocytosis | journal = Physiological Reviews | volume = 92 | issue = 4 | pages = 1915–1964 | year = 2012 | pmid = 23073634

Mechanism

This outline below presents a broad modeling of how Munc-18 is thought to play a role in vesicle docking and fusion, allowing for intentional exocytosis.{{Cite journal | last1 = Rizo | first1 = J. | last2 = Südhof | first2 = T. C. | doi = 10.1146/annurev-cellbio-101011-155818 | title = The Membrane Fusion Enigma: SNAREs, Sec1/Munc18 Proteins, and Their Accomplices—Guilty as Charged? | journal = Annual Review of Cell and Developmental Biology | volume = 28 | pages = 279–308 | year = 2012 | pmid = 23057743

  1. Munc18-1 binds to a closed form of syntaxin-1, blocking SNARE complex formation. This is thought to affect vesicle docking
  2. Munc13 opens syntaxin-1, Munc18-1 is translocated to the SNARE complex, which releases the inhibitory effect, allowing assembly (specifically of the alpha helix 4 part bundle)
  3. It is thought that Munc18-1 stabilizes the formed trans-SNARE complex, preventing its dissociation
  4. The SNARE complex, potentially with the assistance of Munc-18 brings the membranes together and causes fusion

It has also been shown in one study that Munc-18 binds to the C-terminus of synaptobrevin, suggesting that this protein plays an important role in membrane fusion.

Family members

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

::data[format=table]

proteingenesymbolname
MUNC18-1STXBP1syntaxin binding protein 1
MUNC18-2STXBP2syntaxin binding protein 2
MUNC18-3STXBP3syntaxin binding protein 3
MUNC18-4STXBP4syntaxin binding protein 4
MUNC18-5STXBP5syntaxin binding protein 5
MUNC18-6STXBP6syntaxin binding protein 6
::

References

References

  1. (1992). "The unc-18 Gene Encodes a Novel Protein Affecting the Kinetics of Acetylcholine Metabolism in the Nematode Caenorhabditis elegans". Journal of Neurochemistry.
  2. (May 1974). "The Genetics of Caenorhabditis Elegans". Genetics.
  3. (October 2006). "Munc18-bound syntaxin readily forms SNARE complexes with synaptobrevin in native plasma membranes". PLOS Biol..
  4. (August 1994). "Specificity and regulation of a synaptic vesicle docking complex". Neuron.
  5. (2009). "The functions of Munc18-1 in regulated exocytosis.". Ann N Y Acad Sci.
  6. (March 2010). "Single-Vesicle Fusion Assay Reveals Munc18-1 Binding to the SNARE Core Is Sufficient for Stimulating Membrane Fusion.". ACS Chem Neurosci.
  7. (June 2005). "Munc18-1 stabilizes syntaxin 1, but is not essential for syntaxin 1 targeting and SNARE complex formation". J. Neurochem..
  8. "Members :: Network of European Neuroscience Institutes".
  9. (2 March 2010). "Binding of Munc18-1 to synaptobrevin and to the SNARE four-helix bundle.". Biochemistry.

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neurophysiologyhuman-proteins