Munc-18 (an

acronym An acronym is a word or name formed from the initial components of a longer name or phrase. Acronyms are usually formed from the initial letters of words, as in ''NATO'' (''North Atlantic Treaty Organization''), but sometimes use syllables, as ...

for mammalian uncoordinated-18) proteins are the mammalian homologue of UNC-18 (which was first discovered in the nematode worm

C. elegans ''Caenorhabditis elegans'' () is a free-living transparent nematode about 1 mm in length that lives in temperate soil environments. It is the type species of its genus. The name is a blend of the Greek ''caeno-'' (recent), ''rhabditis'' (r ...

) 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 Exocytosis () is a form of active transport and bulk transport in which a cell transports molecules (e.g., neurotransmitters and proteins) out of the cell ('' exo-'' + ''cytosis''). As an active transport mechanism, exocytosis requires the use o ...

neuron A neuron, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa. N ...

s and

neuroendocrine cell Neuroendocrine cells are cells that receive neuronal input (through neurotransmitters released by nerve cells or neurosecretory cells) and, as a consequence of this input, release messenger molecules ( hormones) into the blood. In this way they b ...

Function

Munc-18 binds

syntaxin Syntaxins are a family of membrane integrated Q-SNARE proteins participating in exocytosis. Domains Syntaxins possess a single C-terminal transmembrane domain, a SNARE domain (known as H3), and an N-terminal regulatory domain (Habc). Syntaxin ...

and forms a syntaxin/munc-18 complex which is thought to precede and/or regulate vesicle priming, a process mediated by

VAMP The VaMP driverless car was one of the first truly autonomous cars Dynamic Vision for Perc ...

SNAP-25 Synaptosomal-Associated Protein, 25kDa (SNAP-25) is a Target Soluble NSF (''N''-ethylmaleimide-sensitive factor) Attachment Protein Receptor (t-SNARE) protein encoded by the ''SNAP25'' gene found on chromosome 20p12.2 in humans. SNAP-25 is a comp ...

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 The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or amine-terminus) is the start of a protein or polypeptide, referring to the free amine group (-NH2) located at the end of a polypeptide. Within a peptide, the ami ...

of syntaxin, causes a conformation change, activating syntaxin, which in turn connects to the ternary- SNARE complex. Deletion of munc18-1 leads to a defect in secretory vesicle docking. 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."

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

. As it is a combined preliminary modeling, more research is necessary to fully understand the role of Munc-18 in this process. #Munc18-1 binds to a closed form of

-1, blocking SNARE complex formation. This is thought to affect vesicle docking #Munc13 opens

-1, Munc18-1 is translocated to the SNARE complex, which releases the inhibitory effect, allowing assembly (specifically of the alpha helix 4 part bundle) #It is thought that Munc18-1 stabilizes the formed trans-SNARE complex, preventing its dissociation #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 Synaptobrevins (''synaptobrevin isotypes 1-2'') are small integral membrane proteins of secretory vesicles with molecular weight of 18 kilodalton (kDa) that are part of the vesicle-associated membrane protein (VAMP) family. Synaptobrevi ...

, suggesting that this protein plays an important role in membrane fusion.

Family members

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

References

External links

* {{Vesicular transport proteins Neurophysiology Human proteins

Function

Mechanism

Family members

See also

References

External links