![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Vol. 17, Issue 10, 4300-4317, October 2006
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
*Department of Cell Biology and Physiology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261; and Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO 63110
Submitted May 16, 2006;
Revised July 18, 2006;
Accepted July 19, 2006
Monitoring Editor: Sandra Schmid
Sorting of transmembrane cargo into clathrin-coated vesicles requires endocytic adaptors, yet RNA interference (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.
The online version of this contains supplemental material at MBC Online (http://www.molbiolcell.org). This article was published online ahead of print in MBC in Press (http://www.molbiolcell.org/cgi/doi/10.1091/mbc.E06-05-0421) on July 26, 2006.
Address correspondence to: Linton M. Traub (traub{at}pitt.edu)
This article has been cited by other articles:
|
|
 |
|
  A. Tuli, M. Sharma, H. L. Capek, N. Naslavsky, S. Caplan, and J. C. Solheim Mechanism for Amyloid Precursor-like Protein 2 Enhancement of Major Histocompatibility Complex Class I Molecule Degradation J. Biol. Chem., December 4, 2009; 284(49): 34296 - 34307. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. J. Ezratty, C. Bertaux, E. E. Marcantonio, and G. G. Gundersen Clathrin mediates integrin endocytosis for focal adhesion disassembly in migrating cells J. Cell Biol., November 30, 2009; 187(5): 733 - 747. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Teckchandani, N. Toida, J. Goodchild, C. Henderson, J. Watts, B. Wollscheid, and J. A. Cooper Quantitative proteomics identifies a Dab2/integrin module regulating cell migration J. Cell Biol., July 13, 2009; 186(1): 99 - 111. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. R. Thieman, S. K. Mishra, K. Ling, B. Doray, R. A. Anderson, and L. M. Traub Clathrin Regulates the Association of PIPKI{gamma}661 with the AP-2 Adaptor {beta}2 Appendage J. Biol. Chem., May 15, 2009; 284(20): 13924 - 13939. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Martin-Acebes, M. Gonzalez-Magaldi, A. Vazquez-Calvo, R. Armas-Portela, and F. Sobrino Internalization of Swine Vesicular Disease Virus into Cultured Cells: a Comparative Study with Foot-and-Mouth Disease Virus J. Virol., May 1, 2009; 83(9): 4216 - 4226. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. W. Lau and M. M. Chou The adaptor complex AP-2 regulates post-endocytic trafficking through the non-clathrin Arf6-dependent endocytic pathway J. Cell Sci., December 15, 2008; 121(24): 4008 - 4017. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. A. Keyel, J. R. Thieman, R. Roth, E. Erkan, E. T. Everett, S. C. Watkins, J. E. Heuser, and L. M. Traub The AP-2 Adaptor {beta}2 Appendage Scaffolds Alternate Cargo Endocytosis Mol. Biol. Cell, December 1, 2008; 19(12): 5309 - 5326. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Zhao and P. Michaely The Epidermal Growth Factor Homology Domain of the LDL Receptor Drives Lipoprotein Release through an Allosteric Mechanism Involving H190, H562, and H586 J. Biol. Chem., September 26, 2008; 283(39): 26528 - 26537. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Chen and X. Zhuang Epsin 1 is a cargo-specific adaptor for the clathrin-mediated endocytosis of the influenza virus PNAS, August 19, 2008; 105(33): 11790 - 11795. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. S. Pandey, E. N. Harris, J. A. Weigel, and P. H. Weigel The Cytoplasmic Domain of the Hyaluronan Receptor for Endocytosis (HARE) Contains Multiple Endocytic Motifs Targeting Coated Pit-mediated Internalization J. Biol. Chem., August 1, 2008; 283(31): 21453 - 21461. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Lehtonen, M. Shah, R. Nielsen, N. Iino, J. J. Ryan, H. Zhou, and M. G. Farquhar The Endocytic Adaptor Protein ARH Associates with Motor and Centrosomal Proteins and Is Involved in Centrosome Assembly and Cytokinesis Mol. Biol. Cell, July 1, 2008; 19(7): 2949 - 2961. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. K. Mishra, A. Jha, A. L. Steinhauser, V. A. Kokoza, C. H. Washabaugh, A. S. Raikhel, W. A. Foster, and L. M. Traub Internalization of LDL-receptor superfamily yolk-protein receptors during mosquito oogenesis involves transcriptional regulation of PTB-domain adaptors J. Cell Sci., April 15, 2008; 121(8): 1264 - 1274. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Ricotta, J. Hansen, C. Preiss, D. Teichert, and S. Honing Characterization of a Protein Phosphatase 2A Holoenzyme That Dephosphorylates the Clathrin Adaptors AP-1 and AP-2 J. Biol. Chem., February 29, 2008; 283(9): 5510 - 5517. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. R. Eden, X.-M. Sun, D. D. Patel, and A. K. Soutar Adaptor protein Disabled-2 modulates low density lipoprotein receptor synthesis in fibroblasts from patients with autosomal recessive hypercholesterolaemia Hum. Mol. Genet., November 15, 2007; 16(22): 2751 - 2759. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. M. Traub and G. L. Lukacs Decoding ubiquitin sorting signals for clathrin-dependent endocytosis by CLASPs J. Cell Sci., February 15, 2007; 120(4): 543 - 553. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. E. Maurer and J. A. Cooper The adaptor protein Dab2 sorts LDL receptors into coated pits independently of AP-2 and ARH J. Cell Sci., October 15, 2006; 119(20): 4235 - 4246. [Abstract] [Full Text] [PDF]
|
|
