Regulation of GPCRs by Membrane Trafficking and Its Potential Implications. Export

@article{citeulike:1805362, abstract = {blacksquare, square, filled Abstract The endocytic pathway tightly controls the activity of G protein-coupled receptors (GPCRs). Ligand-induced endocytosis can drive receptors into divergent lysosomal and recycling pathways, producing essentially opposite effects on the strength and duration of cellular signaling via heterotrimeric G proteins, and may also promote distinct signaling events from intracellular membranes. This chapter reviews recent developments toward understanding the molecular machinery and functional implications of GPCR sorting in the endocytic pathway, focusing on mammalian GPCRs whose ligandinduced endocytosis is mediated primarily by clathrin-coated pits. Lysosomal sorting of a number of GPCRs occurs via a highly conserved mechanism requiring covalent tagging of receptors with ubiquitin. There is increasing evidence that additional, noncovalent mechanisms control the sorting of endocytosed GPCRs to lysosomes in mammalian cells. Recycling of several GPCRs to the plasma membrane is also specifically sorted, via a mechanism requiring both receptor-specific and shared sorting proteins. The current data reveal an unprecedented degree of specificity and plasticity in the cellular regulation of mammalian GPCRs by endocytic membrane trafficking. These developments have fundamental implications for GPCR pharmacology, and suggest new mechanisms that could be exploited in GPCR-directed pharmacotherapy. Expected final online publication date for the Annual Review of Pharmacology and Toxicology Volume 48 is January 6, 2008. Please see http://www.annualreviews.org/catalog/pubdates.aspx for revised estimates.}, address = {Institute of Reproductive Biology and Development, Imperial College London, Hammersmith Campus, London, W12 0NN, United Kingdom.}, author = {Hanyaloglu, Aylin C C. and von Zastrow, Mark}, citeulike-article-id = {1805362}, citeulike-linkout-0 = {http://dx.doi.org/10.1146/annurev.pharmtox.48.113006.094830}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/17937597}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=17937597}, day = {15}, doi = {10.1146/annurev.pharmtox.48.113006.094830}, issn = {0362-1642}, journal = {Annu Rev Pharmacol Toxicol}, keywords = {gpcrs, review}, month = {October}, posted-at = {2009-06-23 01:15:10}, priority = {2}, title = {Regulation of GPCRs by Membrane Trafficking and Its Potential Implications.}, url = {http://dx.doi.org/10.1146/annurev.pharmtox.48.113006.094830}, year = {2007} }

TY - JOUR ID - citeulike:1805362 L3 - citeulike-article-id:1805362 N2 - blacksquare, square, filled Abstract The endocytic pathway tightly controls the activity of G protein-coupled receptors (GPCRs). Ligand-induced endocytosis can drive receptors into divergent lysosomal and recycling pathways, producing essentially opposite effects on the strength and duration of cellular signaling via heterotrimeric G proteins, and may also promote distinct signaling events from intracellular membranes. This chapter reviews recent developments toward understanding the molecular machinery and functional implications of GPCR sorting in the endocytic pathway, focusing on mammalian GPCRs whose ligandinduced endocytosis is mediated primarily by clathrin-coated pits. Lysosomal sorting of a number of GPCRs occurs via a highly conserved mechanism requiring covalent tagging of receptors with ubiquitin. There is increasing evidence that additional, noncovalent mechanisms control the sorting of endocytosed GPCRs to lysosomes in mammalian cells. Recycling of several GPCRs to the plasma membrane is also specifically sorted, via a mechanism requiring both receptor-specific and shared sorting proteins. The current data reveal an unprecedented degree of specificity and plasticity in the cellular regulation of mammalian GPCRs by endocytic membrane trafficking. These developments have fundamental implications for GPCR pharmacology, and suggest new mechanisms that could be exploited in GPCR-directed pharmacotherapy. Expected final online publication date for the Annual Review of Pharmacology and Toxicology Volume 48 is January 6, 2008. Please see http://www.annualreviews.org/catalog/pubdates.aspx for revised estimates. JF - Annu Rev Pharmacol Toxicol SN - 0362-1642 AD - Institute of Reproductive Biology and Development, Imperial College London, Hammersmith Campus, London, W12 0NN, United Kingdom. TI - Regulation of GPCRs by Membrane Trafficking and Its Potential Implications. KW - gpcrs KW - review AU - Hanyaloglu, Aylin C AU - von Zastrow, Mark PY - 2007/10/15/ UR - http://dx.doi.org/10.1146/annurev.pharmtox.48.113006.094830 ER -