JBC Avanti Polar Lipids

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Originally published In Press as doi:10.1074/jbc.M002886200 on September 11, 2000

J. Biol. Chem., Vol. 275, Issue 49, 38176-38181, December 8, 2000
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
275/49/38176    most recent
M002886200v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
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 Sousa, M. M.
Right arrow Articles by Saraiva, M. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Sousa, M. M.
Right arrow Articles by Saraiva, M. J.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Evidence for the Role of Megalin in Renal Uptake of Transthyretin*

Mónica Mendes Sousaabc, Anthony G. W. Nordend, Christian Jacobsene, Thomas E. Willnowf, Erik Ilsø Christenseng, Raj V. Thakkerh, Pierre J. Verrousti, Søren K. Moestrupe, and Maria Joaõ Saraivaabj

From the a Amyloid Unit, Instituto de Biologia Molecular e Celular and the b Instituto de Ciências Biomédicas Abel Salazar, University of Porto, Porto 4150, Portugal, the d Department of Clinical Biochemistry, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2QR, United Kingdom, the Departments of e Medical Biochemistry and g Cell Biology, University of Aarhus, 8000 Aarhus C, Denmark, the f Max-Delbrueck Center for Molecular Medicine, 13125 Berlin, Germany, the h Molecular Endocrinology Group, Nuffield Department of Medicine, University of Oxford, Oxford OX3 9DU, United Kingdom, and the i INSERM, U489, Hôpital Tenon, F-75020 Paris, France

The kidney is a major organ for uptake of the thyroid hormone thyroxine (T4) and its conversion to the active form, triiodothyronine. In the plasma, one of the T4 carriers is transthyretin (TTR). In the present study we observed that TTR, the transporter of both T4 and retinol-binding protein, binds to megalin, the multiligand receptor expressed on the luminal surface of various epithelia including the renal proximal tubules. In the kidney, megalin plays an important role in tubular uptake of macromolecules filtered through the glomerulus. To evaluate the importance of megalin for renal uptake of TTR, we performed binding/uptake assays using immortalized rat yolk sac cells with high expression levels of megalin. Radiolabeled TTR, free as well as in complex with thyroxine or retinol-binding protein, was rapidly taken up by the cells, and the uptake was strongly inhibited by a polyclonal megalin antibody and by the receptor-associated protein, a chaperone-like protein inhibiting ligand binding to megalin. In cell culture, different TTR mutations presented different levels of cell association and degradation, suggesting that the structure of TTR is important for megalin recognition. Both the apo form and the T4-bound form were taken up by the cells. Analysis of urine from patients with Dent's disease, a renal tubular disorder that alters receptor-mediated endocytic reabsorption of proteins, identified TTR as an abundant excreted protein. Furthermore, analysis of kidney sections of megalin-deficient mice revealed no immunohistochemical TTR labeling in intracellular vesicles in the proximal tubule cells when compared with wild type control littermates. Taken together, the present data indicate that TTR represents a novel megalin ligand of importance in the thyroid hormone homeostasis.

* This work was supported by grants from PRAXIS XXI (2/2.1/BIA/459/94) from Portugal (to M. J. S.), the Novo Nordisk Foundation, the Danish Biotechnology Program, and the University of Aarhus (to S. K. M.), and the Sir Jules Thorn Charitable Fund (to A. G. W. N.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

c  Recipient of a post-doctoral fellowship (PRAXIS XXI/BPD/22027/99) from Fundação para a Ciência e Tecnologia (Portugal).

j  To whom correspondence should be addressed: Amyloid Unit, Instituto de Biologia Molecular e Celular, Rua do Campo Alegre 823, Porto 4150, Portugal. Tel.: 351-22-6074900; Fax: 351-22-6099157; E-mail: mjsaraiv@ibmc.up.pt.

Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.
Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
 Am. J. Physiol. Renal Physiol.Home page
A. Vilasi, P. R. Cutillas, A. D. Maher, S. F. M. Zirah, G. Capasso, A. W. G. Norden, E. Holmes, J. K. Nicholson, and R. J. Unwin
Combined proteomic and metabonomic studies in three genetic forms of the renal Fanconi syndrome
Am J Physiol Renal Physiol, August 1, 2007; 293(2): F456 - F467.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. ProteomicsHome page
H. Meistermann, J. L. Norris, H.-R. Aerni, D. S. Cornett, A. Friedlein, A. R. Erskine, A. Augustin, M. C. De Vera Mudry, S. Ruepp, L. Suter, et al.
Biomarker Discovery by Imaging Mass Spectrometry: Transthyretin is a Biomarker for Gentamicin-induced Nephrotoxicity in Rat
Mol. Cell. Proteomics, October 1, 2006; 5(10): 1876 - 1886.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
B. McKinnon, H. Li, K. Richard, and R. Mortimer
Synthesis of Thyroid Hormone Binding Proteins Transthyretin and Albumin by Human Trophoblast
J. Clin. Endocrinol. Metab., December 1, 2005; 90(12): 6714 - 6720.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
E. Carro, C. Spuch, J. L. Trejo, D. Antequera, and I. Torres-Aleman
Choroid Plexus Megalin Is Involved in Neuroprotection by Serum Insulin-Like Growth Factor I
J. Neurosci., November 23, 2005; 25(47): 10884 - 10893.
[Abstract] [Full Text] [PDF]

Home page
 J. Nutr.Home page
J. Raila, T. E. Willnow, and F. J. Schweigert
Megalin-Mediated Reuptake of Retinol in the Kidneys of Mice Is Essential for Vitamin A Homeostasis
J. Nutr., November 1, 2005; 135(11): 2512 - 2516.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
P. R. Cutillas, R. J. Chalkley, K. C. Hansen, R. Cramer, A. G. W. Norden, M. D. Waterfield, A. L. Burlingame, and R. J. Unwin
The urinary proteome in Fanconi syndrome implies specificity in the reabsorption of proteins by renal proximal tubule cells
Am J Physiol Renal Physiol, September 1, 2004; 287(3): F353 - F364.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
M. A. Liz, C. J. Faro, M. J. Saraiva, and M. M. Sousa
Transthyretin, a New Cryptic Protease
J. Biol. Chem., May 14, 2004; 279(20): 21431 - 21438.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
A. Saito, J. J. Kazama, N. Iino, K. Cho, N. Sato, H. Yamazaki, Y. Oyama, T. Takeda, R. A. Orlando, F. Shimizu, et al.
Bioengineered Implantation of Megalin-Expressing Cells: A Potential Intracorporeal Therapeutic Model for Uremic Toxin Protein Clearance in Renal Failure
J. Am. Soc. Nephrol., August 1, 2003; 14(8): 2025 - 2032.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
J. Yang, K. Mori, J. Y. Li, and J. Barasch
Iron, lipocalin, and kidney epithelia
Am J Physiol Renal Physiol, July 1, 2003; 285(1): F9 - F18.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
A. Saito, R. Nagai, A. Tanuma, H. Hama, K. Cho, T. Takeda, Y. Yoshida, T. Toda, F. Shimizu, S. Horiuchi, et al.
Role of Megalin in Endocytosis of Advanced Glycation End Products: Implications for a Novel Protein Binding to Both Megalin and Advanced Glycation End Products
J. Am. Soc. Nephrol., May 1, 2003; 14(5): 1123 - 1131.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
C. Schmitz, J. Hilpert, C. Jacobsen, C. Boensch, E. I. Christensen, F. C. Luft, and T. E. Willnow
Megalin Deficiency Offers Protection from Renal Aminoglycoside Accumulation
J. Biol. Chem., January 4, 2002; 277(1): 618 - 622.
[Abstract] [Full Text]

Home page
 Am. J. Physiol. Renal Physiol.Home page
E. I. Christensen and H. Birn
Megalin and cubilin: synergistic endocytic receptors in renal proximal tubule
Am J Physiol Renal Physiol, April 1, 2001; 280(4): F562 - F573.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
M. M. Sousa and M. J. Saraiva
Internalization of Transthyretin. EVIDENCE OF A NOVEL YET UNIDENTIFIED RECEPTOR-ASSOCIATED PROTEIN (RAP)-SENSITIVE RECEPTOR
J. Biol. Chem., April 20, 2001; 276(17): 14420 - 14425.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 All ASBMB Journals   Molecular and Cellular Proteomics 
 Journal of Lipid Research   ASBMB Today 
Copyright © 2000 by the American Society for Biochemistry and Molecular Biology.