Molecular Biology of the Cell click for CBE Life Science Education Page

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

Originally published as MBC in Press, 10.1091/mbc.E03-06-0385 on October 3, 2003

Vol. 14, Issue 12, 4984-4996, December 2003

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
E03-06-0385v1
14/12/4984    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Nagai, M.
Right arrow Articles by Farquhar, M. G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Nagai, M.
Right arrow Articles by Farquhar, M. G.

The Adaptor Protein ARH Escorts Megalin to and through Endosomes

Masaaki Nagai *, Timo Meerloo *, Tetsuro Takeda *, and Marilyn Gist Farquhar * {dagger} {ddagger}

* Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, California 92093; {dagger} Department of Pathology, University of California, San Diego, La Jolla, California 92093

Submitted June 10, 2003; Revised August 8, 2003; Accepted August 18, 2003
Monitoring Editor: Juan Bonifacino

Megalin is an endocytic receptor that binds multiple ligands and is essential for many physiological processes such as brain development and uptake of proteins by the kidney tubule, yolk sac, and thyroid. The cytoplasmic tail of megalin contains two FXNPXY motifs. Autosomal recessive hypercholesterolemia (ARH) is an adaptor protein that binds to the FXNPXY motif of the low-density lipoprotein receptor as well as clathrin and AP-2. We found that ARH also binds to the first FXNPXY motif of megalin in two-hybrid, pull-down and coimmunoprecipitation assays. ARH colocalizes with megalin in clathrin coated pits and in recycling endosomes in the Golgi region. When cells are treated with nocodazole, the recycling endosomes containing megalin and ARH disperse. On internalization of megalin, ARH and megalin are first seen in clathrin coated pits followed by sequential localization in early endosomes and tubular recycling endosomes in the pericentriolar region followed by their reappearance at the cell surface. Expression of ARH in Madin-Darby canine kidney cells expressing megalin mini-receptors enhances megalin-mediated uptake of 125I-lactoferrin, a megalin ligand. These results show that ARH facilitates endocytosis of megalin, escorts megalin along its endocytic route and raise the possibility that transport through the endosomal system is selective and requires interaction with specific adaptor proteins.

{ddagger} Corresponding author. E-mail address: mfarquhar{at}ucsd.edu.




This article has been cited by other articles:


Home page
 J. Biol. Chem.Home page
T. Tang, B. Zheng, S.-h. Chen, A. N. Murphy, K. Kudlicka, H. Zhou, and M. G. Farquhar
hNOA1 Interacts with Complex I and DAP3 and Regulates Mitochondrial Respiration and Apoptosis
J. Biol. Chem., February 20, 2009; 284(8): 5414 - 5424.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Biol. CellHome page
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]

Home page
 J. Cell Sci.Home page
A. Holmes, A. Flett, D. Coudreuse, H. C. Korswagen, and J. Pettitt
C. elegans Disabled is required for cell-type specific endocytosis and is essential in animals lacking the AP-3 adaptor complex
J. Cell Sci., August 1, 2007; 120(15): 2741 - 2751.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
B. Zheng, T. Tang, N. Tang, K. Kudlicka, K. Ohtsubo, P. Ma, J. D. Marth, M. G. Farquhar, and E. Lehtonen
Essential role of RGS-PX1/sorting nexin 13 in mouse development and regulation of endocytosis dynamics
PNAS, November 7, 2006; 103(45): 16776 - 16781.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Sci.Home page
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]

Home page
 Am. J. Physiol. Renal Physiol.Home page
H. Birn
The kidney in vitamin B12 and folate homeostasis: characterization of receptors for tubular uptake of vitamins and carrier proteins
Am J Physiol Renal Physiol, July 1, 2006; 291(1): F22 - F36.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
J. Nagai, E. I. Christensen, S. M. Morris, T. E. Willnow, J. A. Cooper, and R. Nielsen
Mutually dependent localization of megalin and Dab2 in the renal proximal tubule
Am J Physiol Renal Physiol, September 1, 2005; 289(3): F569 - F576.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
D. H. Hryciw, C. A. Pollock, and P. Poronnik
PKC-{alpha}-mediated remodeling of the actin cytoskeleton is involved in constitutive albumin uptake by proximal tubule cells
Am J Physiol Renal Physiol, June 1, 2005; 288(6): F1227 - F1235.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
S. Schmieder, M. Nagai, R. A. Orlando, T. Takeda, and M. G. Farquhar
Podocalyxin Activates RhoA and Induces Actin Reorganization through NHERF1 and Ezrin in MDCK Cells
J. Am. Soc. Nephrol., September 1, 2004; 15(9): 2289 - 2298.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
Copyright © 2003 by The American Society for Cell Biology. Terms of copyright protection, warranties, and disclaimers.