New Modes of GPCR Signalling

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ABSTRACT TRPA1: a Sentinel for Noxious Chemicals and Temperatures Craig Montell Department of Biological Chemistry, The Johns Hopkins University School of Medicine TRP channels endow us with the ability to sense tastants, mechanical stimuli, a variety of chemicals, distinct temperatures and in some animals, light and pheromones. In this seminar, I will begin with the identification of the founding member of the TRP family, which functions in fly phototransduction, and the realization that TRP channels are global and evolutionarily conserved mediators of sensory signaling in all animals. I will describe our recent studies demonstrating that the ability of Drosophila larva to discriminate between the optimal temperature of 18°C and slightly higher temperatures depends on the TRPA1 channel, which functions downstream of a phototransduction-like cascade. We propose that activation of TRPA1 via a signaling cascade, rather than through direct thermal activation, promotes amplification of small differences in temperature and facilitates adaptation to temperatures within the comfortable range. I will summarize our work demonstrating that insect TRPA1 is a target for insect repellents. Our studies identifies insect TRPA1 as a potential target for developing improved repellents to reduce insect-borne diseases such as malaria, which cause significant morbidity and mortality.
INVITED SPEAKER’S INFO Prof. Huaxi Xu PhD, Professor and Acting Director Neurodegenerative Disease Program Center for Neuroscience, Stem Cell and Aging Research Burnham Institute for Medical Research 10901 N. Torrey Pines Road La Jolla, California 92037. Tel: 858-795-5246 Fax:858-597-5273 E-mail: xuh@burnham.org Education 1981-1985 Xiamen University, China. B.S. in Biochemistry. 1987-1988 Visiting Scholar. Division of Rheumatology. University of Connecticut Health Center, Farmington, CT. 1988-1993 Ph.D. Dept. of Anatomy and Structural Biology. Albert Einstein College of Medicine, New York. 1993-1994 Post-Doctoral Fellow. Dept.of Developmental and Molecular Biology, Albert Einstein College of Medicine. 1994-1998 Post-Doctoral Associate, Research Associate. The Rockefeller University, New York, NY. Joint Appointment in Dept. of Neurology & Neuroscience, Cornell University Medical College, New York, NY. 1998-2003 Assistant Professor, Fisher Center for Research on Alzheimer Disease, The Rockefeller University, New York, NY. 2003-2008 Associate Professor, Neurodegenerative Disease Program Burnham Institute for Medical Research 2008- Professor and Acting Director,Neurodegenerative Disease Program Burnham Institute for Medical Research Selected Publications 1. Xu, H., Sweeney, D., Greengard, P., and Gandy, S. (1996). Metabolism of Alzheimer ß-Amyloid Precursor Protein: Regulation by Protein Kinase A in Intact Cells and in a Cell-Free System. Proc. Natl. Acad. Sci. USA. 93:4081-4084. 2. Xu, H., Sweeney, D., Wang, R., Thinakaran, G., Lo, A. C. Y., Sisodia, S., Greengard, P., and Gandy, S. (1997) Generation of Alzheimer ß-amyloid Protein in the trans-Golgi Network in the Apparent Absence of Vesicle Formation. Proc. Natl. Acad. Sci. USA. 94:3748-3752. 3. Xu, H., Gouras, G. K., Greenfield, J. P., Vincent, B, Naslund, J., Mazzarelli, L, Jovanovic, J. N, Seeger, M, Relkin, N. R, Liao, F., Checler, F., Buxbaum, J. D, Chait, B. T., Thinakaran, G., Sisodia, S., Wang, R., Greengard, P., and Gandy, S. (1998). Estrogen Reduces Neuronal Generation of Alzheimer ß-amyloid Peptides. Nature.Med 4:447-451.
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