Mathematical Biology Seminar

Villu Maricq
Department of Biology, University of Utah
Wednesday Nov. 22, 2006
3:05pm in LCB 215
Glutamate-Operated Signaling Machines: New Insights from Genetic Analysis

Abstract: C. elegans explores its environment and forages for resources by dynamically modulating its turning frequency. Cell ablation studies and analysis of informative mutants has revealed part of the neural circuitry that controls turning and reversals. Release of glutamate >From sensory neurons, which are required for the avoidance of aversive environmental stimuli and foraging behavior, activates different types of post-synaptic glutamate receptors expressed in interneurons. Depending on the sensory signal, glutamate release leads to the activation of non-NMDA iGluRs, encoded by the glr-1 and glr-2 genes, and NMDARs encoded by the nmr-1 and nmr-2 genes. Worms with mutations that disrupt GLR-1 stability, function or synaptic localization have defective avoidance responses. Foraging, a time and experience dependent behavior, which may reflect more plastic changes in synaptic strength, is also disrupted. We have used a combination of genetic and electrophysiological studies to better understand the development, function and plasticity of glutamatergic synapses. Our genetic studies have revealed that GLR-1 receptors do not form stand- alone functional channels, but rather, are part of a signaling complex that contain at least two other proteins: SOL-1, a CUB-domain transmembrane protein that modulates the rate of GLR-1 desensitization; and STG-1, a tetraspanning transmembrane protein required for GLR-1 function that is related to the vertebrate stargazin (TARP) family of proteins. A concept that has recently emerged is that iGluRs are constantly trafficking in and out of synapses by lateral diffusion in the plasma membrane and by cycling between the cell surface and intracellular organelles. We are using a variety of genetic, electrophysiological and imaging techniques to address whether components of the GLR-1/SOL-1/STG-1 signaling complex are independently regulated, and to determine the contributions of receptor cycling to circuit function and behavior.