Role of RIM and MUNC13 in neuropeptide secretion
The presynaptic proteins RIM and MUNC13 play key roles in release of neurotransmitters from synaptic vesicles (SVs) and neuropeptides from dense-core vesicles (DCVs) but how DCVs are targeted to release sites and whether RIM and MUNC13 are involved in this process is not clear.
The researchers show that three membrane-binding domains in RIM and MUNC13 regulate DCV exocytosis differently from SV exocytosis.
They demonstrate that MUNC13 is essential for DCV exocytosis and RIM N terminus prevents MUNC13 degradation via the proteasome, and inhibiting proteasomal degradation partially rescues DCV exocytosis in RIM’s absence.
The authors also show that the PIP2-binding RIM C2B domain and MUNC13 C1-C2B polybasic face are redundant for DCV exocytosis, while the lipid-binding MUNC13 C2C domain is crucial.
Thus, the study reveal that RIM and MUNC13 synergistically regulate DCV exocytosis through membrane interactions and reveal new mechanistic differences between SV and DCV exocytosis.
https://rupress.org/jcb/article/224/7/e202409196/277919/RIM-and-MUNC13-membrane-binding-domains-are
