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Endocytic membrane traffic and cell signaling

Receptor endocytosis plays important roles in mediating physiological adaptation of many signaling systems, and in determining the longer‐term signaling responsiveness of cells under conditions of prolonged or repeated activation by drugs. We have been engaged in elucidating the mechanistic basis for this regulation, focusing on how receptors are sorted between divergent downstream membrane trafficking fates after endocytosis, and on identifying physiological consequences of this trafficking in the mammalian central nervous system. We have identified a conserved machinery mediating the sorting of internalized G protein‐coupled receptors (GPCRs) into the plasma membrane recycling pathway, and converse regulation of the endocytic machinery by activated signaling receptors. We will discuss these findings and recent progress in developing methods to probe the signaling status of receptors in defined subcellular membrane domains.