Munc13s are homologues of the C. elegans unc-13 gene product. Three brain-specific isoforms, Munc 13-1, -13-2, and -13-3, are expressed in rat, where they localize to presynaptic terminals. All three isoforms share multiple regulatory domains that may mediate phorbol ester and diacylglycerol binding.
Munc13-1 shows the broadest expression pattern and is found in cortex, cerebellum, olfactory bulb, and hippocampus. Munc13-2 is mainly expressed in cortex and hippocampus, whereas Munc13-3 exhibits highest expression levels in cerebellum and pons. Munc13-1 interacts directly with a putative coiled-coil domain in the N-terminal part of syntaxin and is involved in synaptic vesicle priming. For Munc13-2 an additional ubiquitously expressed N-terminal splice variant (ubMunc13-2) has been described.
Munc13-3 has been shown to be involved in the regulation of cerebellar synaptic transmission and motor learning.