Munc133

Munc133, also known as Munc13-3 or UNC13C, is a presynaptic protein that belongs to the Munc13 family of vesicle priming factors in neurons. In humans, UNC13C encodes one of the Munc13 isoforms that contribute to the preparation of synaptic vesicles for rapid neurotransmitter release at chemical synapses.

Structurally, Munc133 proteins typically contain a C1 domain that binds diacylglycerol and phorbol esters, a central MUN domain essential for promoting SNARE complex assembly, and C2 domains that participate in calcium- dependent regulation. This arrangement enables Munc133 to link signaling pathways that regulate vesicle priming to the molecular machinery that drives vesicle fusion.

Functionally, Munc133 promotes the priming of synaptic vesicles by facilitating the correct docking and readiness of vesicles for fusion with the presynaptic membrane. It interacts with core components of the release machinery, including SNARE proteins, and with active-zone scaffolding proteins such as RIM, which helps cluster vesicles at sites of neurotransmitter release. The activity of Munc133 is modulated by calcium signals through its C2 domains and by diacylglycerol through the C1 domain, linking extracellular cues to release probability and short-term plasticity.

Expression patterns of Munc133 are neuronal, with localization to presynaptic terminals. Its function is often studied in relation to other Munc13 family members, as redundancy and compensation can occur among isoforms. Genetic or functional disruption of Munc133 can alter neurotransmitter release and synaptic efficacy, underscoring its role in maintaining efficient synaptic transmission.

See also Munc13 family; UNC13 genes; SNARE complex; presynaptic active zone.