News and Publications

Molecular Mechanisms of Sensory Neuron Specification and Function

A. Patapoutian, T. Earley, S. Eid, T. Hricik, S.W. Huang, X. Liu, A. Moqrich, G. Story

The sensory nervous system in vertebrates enables fine detection of varied external information. The sense of touch consists of the perception of multiple discrete types of stimuli, including temperature, pain, position, and pressure. A great deal remains unknown about the molecular pathways that lead to the diversity of somatic neurons that sense "touch" and the ability of the neurons to detect various stimuli. We are using genomics, imaging, and transgenic technologies to identify and characterize proteins involved in the development and function of these sensory neurons.

A major effort is devoted to identifying molecules that play important roles in the actual detection of various mechanical and thermal stimuli. One molecule involved in such detection is vanilloid receptor 1, which is activated by noxious heat. We cloned novel transient-receptor-potential channels related to vanilloid receptor 1 that are expressed in sensory neurons. One of these, TRPM8, is the first channel known to be activated by cold temperatures and by a cooling agent, menthol. We are characterizing this and other transient-receptor-potential channels relevant to the sensory nervous system.

We are also interested in the mechanisms by which sensory neurons become restricted in function, so that some neurons sense cold temperatures only, whereas others sense mechanical stimulation only. Neurotrophins and their Trk receptors are candidates for a role in this process. We are using (1) transgenic mice that express genes for various neurotrophins to show that neurotrophins play an instructive role during the development of sensory neurons and (2) neurotrophin-deficient mice and expression array methods to identify genes uniquely expressed in distinct classes of sensory neurons in dorsal root ganglia.

Finally, in a collaborative effort with the Genomics Institute of the Novartis Research Foundation, San Diego, California, we are conducting a large-scale induced mutagenesis screen for behavioral phenotypes in mice. A screen for altered sensitivity to pain and temperature is also being conducted.

PUBLICATIONS

Patapoutian, A. Making the pain connection. Neuron 31:4, 2001.

Peier, A.M., Moqrich, A., Hergarden, A.C., Reeve, A.J., Anderson, D.A., Story, G.M., Earley, T.J., Dragoni, I., McIntyre, P., Bevan, S., Patapoutian, A. A TRP channel that senses cold stimuli and menthol. Cell 108:705, 2002.

Su, A.I., Cooke, M.P., Ching, K.A., Hakak, Y., Walker, J.R., Wiltshire, T., Orth, A.P., Vega, R.G., Sapinoso, L.M., Moqrich, A., Patapoutian, A., Hampton, G.M., Schultz, P.G., Hogenesch, J.B. Large-scale analysis of the human and mouse transcriptomes. Proc. Natl. Acad. Sci. U. S. A. 99:4465, 2002.