| Abstract: | ["Neuropeptide signaling is a central factor in brain communication as it controls physiological functions such as brain development, synaptic plasticity, circadian rhythm, many behaviors and emotions. However, while synaptic vesicle release principles are well-characterized, neuropeptide release mechanisms remain largely unknown. In my talk I will show that we have identified the SEC4p ortholog Rab3 and the active-zone protein RIM1 as essential molecules for neuropeptide release in mammalian neurons. Inactivation of all four Rab3 genes ablated 90% of neuropeptide release, which was rescued by expression of Rab3A. In RIM1\/2-deficient neurons neuropeptide release was absent. Expression of RIM1alpha, but not Rab3- or Munc13-binding deficient RIM1, restored secretion in RIMdeficient neurons. Strikingly, a RIM1 truncation that only contains the Rab3 and Munc13-interacting domains co-trafficked with neuropeptide vesicles and rescued secretion. Hence, Rab3, RIM and Munc13 together control neuropeptide secretion. We propose that RIM1 organizes neuropeptide vesicle fusion, also outside synapses, by positioning\/activating Munc13 and recruiting vesicles via Rab3A."] |
