POSTPONED: Killam Seminar Series: Importance of Munc13 in synaptic transmission: New Mechanistic Insights into an Old Problem

**The Killam Seminar on May 2 has been postponed to a later date.

To attend in person, register here.

To watch via vimeo, click here.

Jeremy Dittman

Associate Professor, Biochemistry, Weill Cornell Medicine, United States

Host: Wayne Sossin

Abstract: Munc13 is a deeply conserved synaptic hub protein that coordinates nearly every aspect of neurotransmitter release, although we still lack a mechanistic understanding of its actions at the synapse. Using a forward genetic screen in C. elegans, we identified and characterized a unique C-terminal domain that is critical for maintaining the pool of fusion-competent vesicles at the synapse (the docking/priming function of Munc13). We also determined that a neighboring protein module comprising a C1-C2 tandem domain mediates an autoinhibitory function that is critical for proper regulation of synaptic transmission. A human point mutation in this site leads to severe neurological dysfunction due to a gain of Munc13 activity. Together with recent structural work on Munc13, our biochemical, genetic, and physiological data suggest a principal organizational role for Munc13 in controlling vesicle docking, SNARE assembly, and membrane fusion.

Bio: The long-term goal of our research is to elucidate the molecular mechanisms that underlie both the plasticity and stability of synapses. Synapses are the sites of communication between the individual cells of the brain, and these special connections can be altered by experience, development, and disease. Our lab studies several highly conserved molecules involved in synaptic transmission using cutting-edge imaging and molecular techniques combined with biochemical, physiological, and biophysical assays in the nematode C. elegans as a model system. C. elegans has proven to be a powerful genetic model for the study of essential neuronal proteins because of its amenability to molecular manipulation, fluorescent and electron micrographic imaging, physiological and pharmacological assays, and its simple genetics.

Supported by the generosity of the Killam Trusts, the MNI's Killam Seminar Series invites outstanding guest speakers whose research is of interest to the scientific community at the MNI and McGill University.