syntaxinMunc18

Syntaxin Munc18, also known as STXBP1, is a protein that plays a crucial role in the regulation of neurotransmitter release from synaptic vesicles. It is a component of the SNARE complex, a group of proteins essential for membrane fusion events. STXBP1 specifically binds to syntaxin 1, a transmembrane protein located on the plasma membrane. This interaction is critical for priming and zippering the SNARE complex, which ultimately drives the fusion of synaptic vesicles with the presynaptic membrane, leading to the release of neurotransmitters into the synaptic cleft.

The interaction between STXBP1 and syntaxin 1 is highly regulated. In its closed conformation, syntaxin 1 is unable to interact with other SNARE proteins. STXBP1 acts as a molecular chaperone, binding to syntaxin 1 and holding it in this closed, inhibitory state. Upon arrival of an action potential, a cascade of events leads to the release of STXBP1 from syntaxin 1, allowing syntaxin 1 to adopt an open conformation and engage with other SNARE proteins, SNAP-25 and VAMP2. This precise choreography ensures that neurotransmitter release is tightly controlled and occurs only when and where it is needed. Mutations in the STXBP1 gene have been linked to a range of neurological disorders, including intellectual disability and epilepsy, highlighting its vital importance in neuronal function.