A Single Common Portal for Clathrin-mediated Endocytosis of Distinct Cargo Governed by Cargo-selective Adaptors. Export

@article{citeulike:780750, abstract = {Monitoring Editor: Sandra Schmid Sorting of transmembrane cargo into clathrin-coated vesicles requires endocytic adaptors, yet RNAi-mediated gene silencing of the AP-2 adaptor complex only disrupts internalization of a subset of clathrin-dependent cargo. This suggests alternate clathrin-associated sorting proteins participate in cargo capture at the cell surface and a provocative recent proposal is that discrete endocytic cargo are sorted into compositionally and functionally distinct clathrin coats. We show here that the FXNPXY-type internalization signal within cytosolic domain of the LDL receptor is recognized redundantly by two phosphotyrosine-binding domain proteins, Dab2 and ARH; diminishing both proteins by RNAi leads to conspicuous LDL receptor accumulation at the cell surface. AP-2-dependent uptake of transferrin ensues relatively normally in the absence of Dab2 and ARH, clearly revealing delegation of sorting operations at the bud site. AP-2, Dab2, ARH, transferrin and LDL receptors are all present within the vast majority of clathrin structures at the surface, challenging the general existence of specialized clathrin coats for segregated internalization of constitutively-internalized cargo. However, Dab2 expression is exceptionally low in hepatocytes, likely accounting for the pathological hypercholesterolemia that accompanies ARH loss.}, address = {Department of Cell Biology and Physiology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261; Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO 63110.}, author = {Keyel, Peter A A. and Mishra, Sanjay K K. and Roth, Robyn and Heuser, John E E. and Watkins, Simon C C. and Traub, Linton M M.}, citeulike-article-id = {780750}, citeulike-linkout-0 = {http://dx.doi.org/10.1091/mbc.E06-05-0421}, citeulike-linkout-1 = {http://www.molbiolcell.org/cgi/content/abstract/17/10/4300}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/16870701}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=16870701}, day = {26}, doi = {10.1091/mbc.E06-05-0421}, issn = {1059-1524}, journal = {Mol Biol Cell}, keywords = {clathrin, endocytosis}, month = {July}, posted-at = {2006-11-08 15:36:38}, priority = {2}, title = {A Single Common Portal for Clathrin-mediated Endocytosis of Distinct Cargo Governed by Cargo-selective Adaptors.}, url = {http://dx.doi.org/10.1091/mbc.E06-05-0421}, year = {2006} }

TY - JOUR ID - citeulike:780750 L3 - citeulike-article-id:780750 N2 - Monitoring Editor: Sandra Schmid Sorting of transmembrane cargo into clathrin-coated vesicles requires endocytic adaptors, yet RNAi-mediated gene silencing of the AP-2 adaptor complex only disrupts internalization of a subset of clathrin-dependent cargo. This suggests alternate clathrin-associated sorting proteins participate in cargo capture at the cell surface and a provocative recent proposal is that discrete endocytic cargo are sorted into compositionally and functionally distinct clathrin coats. We show here that the FXNPXY-type internalization signal within cytosolic domain of the LDL receptor is recognized redundantly by two phosphotyrosine-binding domain proteins, Dab2 and ARH; diminishing both proteins by RNAi leads to conspicuous LDL receptor accumulation at the cell surface. AP-2-dependent uptake of transferrin ensues relatively normally in the absence of Dab2 and ARH, clearly revealing delegation of sorting operations at the bud site. AP-2, Dab2, ARH, transferrin and LDL receptors are all present within the vast majority of clathrin structures at the surface, challenging the general existence of specialized clathrin coats for segregated internalization of constitutively-internalized cargo. However, Dab2 expression is exceptionally low in hepatocytes, likely accounting for the pathological hypercholesterolemia that accompanies ARH loss. JF - Mol Biol Cell SN - 1059-1524 AD - Department of Cell Biology and Physiology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261; Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO 63110. TI - A Single Common Portal for Clathrin-mediated Endocytosis of Distinct Cargo Governed by Cargo-selective Adaptors. KW - clathrin KW - endocytosis AU - Keyel, Peter A AU - Mishra, Sanjay K AU - Roth, Robyn AU - Heuser, John E AU - Watkins, Simon C AU - Traub, Linton M PY - 2006/07/26/ UR - http://dx.doi.org/10.1091/mbc.E06-05-0421 ER -