Munc18

Munc18 refers to a family of Sec1/Munc18-like (SM) proteins that regulate SNARE-mediated membrane fusion in eukaryotic cells. In humans, the three known family members are STXBP1 (Munc18-1), STXBP2 (Munc18-2), and STXBP3 (Munc18-3). These proteins are essential components of the cellular machinery that mediates vesicle docking, priming, and fusion with target membranes, particularly at specialized secretory and synaptic sites.

SM proteins, including Munc18, typically bind to syntaxins, a family of t-SNAREs, and influence SNARE complex assembly in a highly regulated manner. Munc18 proteins commonly bind syntaxins in a closed conformation to prevent premature SNARE complex formation, acting as chaperones and regulators of trafficking. They can also promote SNARE complex assembly under appropriate conditions, thereby facilitating vesicle fusion with the plasma membrane. The interaction network often involves syntaxin-1A at neuronal synapses and other syntaxins in secretory pathways, coordinating vesicle docking, priming, and fusion events.

Biological roles vary among family members. Munc18-1 is critical for neurotransmitter release in neurons; loss or mutation severely impairs synaptic transmission. Munc18-2 participates in mucosal and other secretory pathways in non-neuronal cells, and Munc18-3 has roles in various secretory processes, including insulin secretion. Because of their central function in exocytosis, mutations in STXBP genes are linked to human disease: STXBP1 mutations are associated with epileptic encephalopathy and neurodevelopmental disorders, while STXBP2 mutations underlie a form of familial hemophagocytic lymphohistiocytosis.