Characterization of new GPCR signaling mechanisms involving WDR36 and Siva1

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One way that cells communicate with each other is by sending chemical messages. These messages are picked up at the surface of the cells by specialized proteins that we refer to as "receptors". The receptors transduce the chemical messages to the interior of the cells and will induce activation or inactivation of a variety of intracellular proteins called "effectors" that cause changes in the function of the cells. The biggest family of receptors is formed by the G protein-coupled receptors (GPCRs) which transduce signals by the intermediary of a "G protein", hence their name. Through diffferent G proteins, a given GPCR can regulate the activity of various effectors. However, the mechanisms that determine the specificity and efficiency of coupling between a GPCR and its effectors are not well understood. We have discovered that proteins called WDR36 and Siva1 dictate the formation of specific signaling complexes between a GPCR called TPbeta, and particular effectors. The present research program will address in detail the molecular mechanisms involved in the regulation of intracellular signaling pathways by WDR36 and Siva1 that modulate cell physiology.