2007 JASN IMPACT FACTOR 7.111	HOME   AUTHOR INFO   EDITORIAL BOARD   SUBSCRIBE   FEEDBACK   ALERTS   HELP
advanced	CURRENT ISSUE	ARCHIVES	JASN Express	ONLINE SUBMISSION

This Article Full Text Full Text (PDF) All Versions of this Article: ASN.2004110925v1 16/8/2330    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Coudroy, G. Articles by Maurice, M. Search for Related Content PubMed PubMed Citation Articles by Coudroy, G. Articles by Maurice, M.

Contribution of Cubilin and Amnionless to Processing and Membrane Targeting of Cubilin–Amnionless Complex

Gwénaëlle Coudroy^*, Jakub Gburek^*,, Renata Kozyraki^*, Mette Madsen, Germain Trugnan, Søren K. Moestrup, Pierre J. Verroust^* and Michèle Maurice^*

^* INSERM-U538, Saint-Antoine Medical Faculty, Paris, France; Université Pierre et Marie Curie, Paris, France; Department of Pharmaceutical Biochemistry, University of Wroclaw, Wroclaw, Poland; and Department of Medical Biochemistry, University of Aarhus, Aarhus, Denmark

Address correspondence to: Dr. Pierre J. Verroust, INSERM U538, Centre Hospitalier Universitaire Saint Antoine, 27 Rue Chaligny, 75012 Paris, France. Phone: 33-1-4001-1323; Fax: 33-1-4001-1390; verroust{at}ccr.jussieu.fr

Received for publication November 10, 2004. Accepted for publication May 16, 2005.

Cubilin is a peripheral apical membrane receptor for multiple ligands that are taken up in several absorptive epithelia. Recently, amnionless (AMN) was identified to form a functional receptor complex with cubilin. By expression in transfected polarized MDCK cells of AMN and several cubilin fragments, including a functional "mini" version of cubilin, the processing, sorting, and membrane anchoring of the complex to the apical membrane were investigated. The results show that truncation mutants, including the N-terminal domain of cubilin, did not appear at the plasma membrane but instead were retained in the endoplasmic reticulum or partially secreted into the medium. Coexpression with AMN led to efficient transport to the apical cell surface of the cubilin constructs, which included the EGF domains, and prevented release into the medium. AMN co-precipitated with cubilin and co-localized with cubilin at the apical cell surface. Apical sorting was observed for a broad set of nonoverlapping cubilin fragments without the N-terminal region, in the absence of AMN. The preference for apical sorting disappeared when glycosylation was inhibited by tunicamycin. In conclusion, it is shown that both units contribute to the processing of the cubilin–AMN complex to the apical membrane: AMN interacts with the EGF domains of cubilin and is responsible for membrane attachment and export of the complex from the endoplasmic reticulum, whereas the extracellular cubilin molecule is responsible for apical sorting of the complex in a carbohydrate-dependent manner.

This article has been cited by other articles:

				F. Jouret, A. Bernard, C. Hermans, G. Dom, S. Terryn, T. Leal, P. Lebecque, J.-J. Cassiman, B. J. Scholte, H. R. de Jonge, et al. Cystic Fibrosis Is Associated with a Defect in Apical Receptor-Mediated Endocytosis in Mouse and Human Kidney J. Am. Soc. Nephrol., March 1, 2007; 18(3): 707 - 718. [Abstract] [Full Text] [PDF]

				D. Shang, X. W. Zheng, M. Niiya, and X. L. Zheng Apical sorting of ADAMTS13 in vascular endothelial cells and Madin-Darby canine kidney cells depends on the CUB domains and their association with lipid rafts Blood, October 1, 2006; 108(7): 2207 - 2215. [Abstract] [Full Text] [PDF]

				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]

Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673