The rockefeller university

Event Details

Type

Friday Lecture Series

Speaker(s)

Kang Shen, Ph.D., M.P.H., associate professor, department of biological sciences, Stanford University

Speaker bio(s)

The functions of the nervous system are mediated by a precisely patterned network of synaptic connections. While several cell-adhesion and secreted molecules promote the assembly of synapses, the contribution of signals that negatively regulate synaptogenesis is not well understood. Dr. Shen and his lab examined synapse formation in the Caenorhabditis elegans motor neuron DA9, whose presynapses are restricted to a specific segment of its axon. Using forward genetic and candidate screens, they found that several diffusible gradients including Wnts and Netrin act as negative regulators of synapse formation. Transmembrane semaphorins also inhibit synapse formation. Together, these extracellular cues that originate from the environment (surrounding non-neuronal tissues or contacting neurites) pattern the synaptic connections by restricting synapse formation.

How do the extracellular factors affect synapse formation? Presynaptic assembly requires the packaging of requisite proteins into vesicular cargoes in the cell soma, their long-distance microtubule-dependent transport down the axon and finally, their reconstitution into functional complexes at prespecified sites. Despite the identification of several molecules that contribute to these events, the regulatory mechanisms defining such discrete states remain elusive. Dr. Shen's lab reported the characterization of an Arf-like small G protein, ARL-8, required during this process. Arl-8 mutants prematurely accumulate presynaptic cargoes within the proximal axon of several neuronal classes, with a corresponding failure to assemble presynapses distally. This proximal accumulation requires the activity of several molecules known to catalyze presynaptic assembly. Dynamic imaging studies reveal that arl-8 mutant vesicles exhibit an increased tendency to form immotile aggregates during transport. Together, these results suggest that arl-8 promotes a trafficking identity for presynaptic cargoes, facilitating their efficient transport by repressing premature self-association. Identification of genetic modifiers of arl-8 revealed that molecular regulatory pathways are critical in determining the aggregation and assembly of presynaptic material. Antagonizing forces promote trafficking or assembly are finely tuned to achieve the appropriate location and size of synapses.

Dr. Shen will discuss his most recent experiments designed to test the genetic relationship between the extracellular factors and the intracellular mechanisms of synapse formation.

Dr. Shen earned his Ph.D. from Duke University in cell biology in 1999 under the supervision of Tobias Meyer. He then joined Cori Bargmann’s lab at University of California, San Francisco, as a postdoc, and in 2003 Dr. Shen was hired as an assistant professor in the department of biology at Stanford University. He became an investigator at the Howard Hughes Medical Institute in 2008 and was promoted to associate professor with tenure in 2009. Among Dr. Shen's many honors are an Alfred P. Sloan Research Fellowship, the Searle Scholar Award, the March of Dimes Basil O’Connor Award, the Keck Distinguished Young Investigator Award and the Human Frontier Science Program Young Investigator Award.

Open to

Public

Reception

Refreshments, 3:15 p.m. - 3:45 p.m., Abby Lounge

Contact

Gloria Phipps

Phone

(212) 327-8967

Sponsor

Gloria Phipps
(212) 327-8967
phippsg@rockefeller.edu