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The Adaptor Protein ARH Escorts Megalin to and through Endosomes

Nagai, Masaaki, Meerloo, Timo, Takeda, Tetsuro, Farquhar, Marilyn Gist·2003·Molecular Biology of the Cell
DOI 10.1091/mbc.e03-06-0385
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Abstract

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 125 I-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.

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  • The redundant function of Arh with Dab2 may account for the very mild kidney functional defect in the Dab2 null mice.

    “The redundant function of Arh with Dab2 may account for the very mild kidney functional defect in the Dab2 null mice (Nagai et al., 2003).”

    From Endocytosis and Physiology: Insights from Disabled-2 Deficient Mice (2016) · cites this paper as Nagai et al., 2003

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Research works printed but not linked: 53

  1. Altschul, S.F., Gish, W., Miller, W., Myers, E.W., and Lipman, D.J. (1990). Basic local alignment search tool.J. Mol. Biol.215, 403-410. · DOI · Paper page
  2. Boll, W., Rapoport, I., Brunner, C., Modis, Y., Prehn, S., and Kirchhausen, T. (2002). The m2 subunit of the clathrin adaptor AP-2 binds to FDNPVY and YppO sorting signals at distinct sites.Traffic3, 590-600. · DOI · Paper page
  3. Bonifacino, J.S., and Traub, L.M. (2003). Signals for sorting of transmembrane proteins to endosomes and lysosomes.Annu. Rev. Biochem.72,395-447. · DOI · Paper page
  4. Chen, W.J., Goldstein, J.L., and Brown, M.S. (1990). NPXY, a sequence often found in cytoplasmic tails, is required for coated pit-mediated internalization of the low density lipoprotein receptor.J. Biol. Chem.265, 3116-3123. · DOI · Paper page
  5. Christensen, E.I., and Birn, H. (2002). Megalin and cubilin: multifunctional endocytic receptors.Nat. Rev. Mol. Cell. Biol.3, 256-266. · DOI
  6. Christensen, E.I., Birn, H., Verroust, P., and Moestrup, S.K. (1998). Membrane receptors for endocytosis in the renal proximal tubule.Int. Rev. Cytol.180, 237-284. · DOI
  7. Christensen, E.I., and Willnow, T.E. (1999). Essential role of megalin in renal proximal tubule for vitamin homeostasis.J. Am. Soc. Nephrol.10, 2224-2236. · DOI
  8. Collins, R.F., Schreiber, A.D., Grinstein, S., and Trimble, W.S. (2002). Syntaxins 13 and 7 function at distinct steps during phagocytosis.J. Immunol.169, 3250-3256. · DOI
  9. 10.1091/mbc.8.3.517 · DOI
  10. Davis, C.G., Lehrman, M.A., Russell, D.W., Anderson, R.G., Brown, M.S., and Goldstein, J.L. (1986). The J. D. mutation in familial hypercholesterolemia: amino acid substitution in cytoplasmic domain impedes internalization of LDL receptors.Cell45, 15-24. · DOI · Paper page
  11. Eden, E.R., Patel, D.D., Sun, X.M., Burden, J.J., Themis, M., Edwards, M., Lee, P., Neuwirth, C., Naoumova, R.P., and Soutar, A.K. (2002). Restoration of LDL receptor function in cells from patients with autosomal recessive hypercholesterolemia by retroviral expression of ARH1.J. Clin. Investig.110, 1695-1702. · DOI · Paper page
  12. Farquhar, M.G., Saito, A., Kerjaschki, D., and Orlando, R.A. (1995). The Heymann nephritis antigenic complex: megalin (gp330) and RAP.J. Am. Soc. Nephrol.6, 35-47. · DOI
  13. Finer, M.H., Dull, T.J., Qin, L., Farson, D., and Roberts, M.R. (1994). kat: a high-efficiency retroviral transduction system for primary human T lymphocytes.Blood83, 43-50. · DOI
  14. Garcia, C.K.et al. (2001). Autosomal recessive hypercholesterolemia caused by mutations in a putative LDL receptor adaptor protein.Science292, 1394-1398. · DOI · Paper page
  15. Goldstein, J.L., Basu, S.K., and Brown, M.S. (1983). Receptor-mediated endocytosis of low-density lipoprotein in cultured cells.Methods Enzymol.98, 241-260. · DOI
  16. Gotthardt, M., Trommsdorff, M., Nevitt, M.F., Shelton, J., Richardson, J.A., Stockinger, W., Nimpf, J., and Herz, J. (2000). Interactions of the low density lipoprotein receptor gene family with cytosolic adaptor and scaffold proteins suggest diverse biological functions in cellular communication and signal transduction.J. Biol. Chem.275, 25616-25624. · DOI · Paper page
  17. Gruenberg, J., and Maxfield, F.R. (1995). Membrane transport in the endocytic pathway.Curr. Opin. Cell Biol.7, 552-563. · DOI
  18. Hopkins, C.R., Gibson, A., Shipman, M., Strickland, D.K., and Trowbridge, I.S. (1994). In migrating fibroblasts, recycling receptors are concentrated in narrow tubules in the pericentriolar area, and then routed to the plasma membrane of the leading lamella.J. Cell Biol.125, 1265-1274. · DOI
  19. Hopkins, C.R., and Trowbridge, I.S. (1983). Internalization and processing of transferrin and the transferrin receptor in human carcinoma A431 cells.J. Cell Biol.97, 508-521. · DOI
  20. Hung, A.Y., and Sheng, M. (2002). PDZ domains: structural modules for protein complex assembly.J. Biol. Chem.277, 5699-5702. · DOI
  21. Kerjaschki, D., and Farquhar, M.G. (1983). Immunocytochemical localization of the Heymann nephritis antigen (GP330) in glomerular epithelial cells of normal Lewis rats.J. Exp. Med.157, 667-686. · DOI
  22. Kerjaschki, D., Noronha-Blob, L., Sacktor, B., and Farquhar, M.G. (1984). Microdomains of distinctive glycoprotein composition in the kidney proximal tubule brush border.J. Cell Biol.98, 1505-1513. · DOI
  23. Kirchhausen, T. (2002). Clathrin adaptors really adapt.Cell109, 413-416. · DOI
  24. Lavoie, C., Meerloo, T., Lin, P., and Farquhar, M.G. (2002). Calnuc, an EF-hand Ca(2+)-binding protein, is stored and processed in the Golgi and secreted by the constitutive-like pathway in AtT20 cells.Mol. Endocrinol.16, 2462-2474. · DOI
  25. Lou, X., McQuistan, T., Orlando, R.A., and Farquhar, M.G. (2002). GAIP, GIPC and Galphai3 are concentrated in endocytic compartments of proximal tubule cells: putative role in regulating megalin's function.J. Am. Soc. Nephrol.13, 918-927. · DOI
  26. Mammoto, A., Ohtsuka, T., Hotta, I., Sasaki, T., and Takai, Y. (1999). Rab11BP/Rabphilin-11, a downstream target of rab11 small G protein implicated in vesicle recycling.J. Biol. Chem.274, 25517-25524. · DOI
  27. Matteoni, R., and Kreis, T.E. (1987). Translocation and clustering of endosomes and lysosomes depends on microtubules.J. Cell Biol.105, 1253-1265. · DOI
  28. McCarthy, R.A., Barth, J.L., Chintalapudi, M.R., Knaak, C., and Argraves, W.S. (2002). Megalin functions as an endocytic sonic hedgehog receptor.J. Biol. Chem.277, 25660-25667. · DOI
  29. Mishra, S.K., Watkins, S.C., and Traub, L.M. (2002b). The autosomal recessive hypercholesterolemia (ARH) protein interfaces directly with the clathrin-coat machinery.Proc. Natl. Acad. Sci. USA99, 16099-16104. · DOI · Paper page
  30. Morris, S.M., and Cooper, J.A. (2001). Disabled-2 colocalizes with the LDLR in clathrin-coated pits and interacts with AP-2.Traffic2, 111-123. · DOI · Paper page
  31. Morris, S.M., Tallquist, M.D., Rock, C.O., and Cooper, J.A. (2002). Dual roles for the Dab2 adaptor protein in embryonic development and kidney transport.EMBO J.21, 1555-1564. · DOI · Paper page
  32. Nagai, M., Meerloo, T., Takeda, T., and Farquhar, M.G. (2003). The adaptor protein ARH escorts megalin through recycling dense apical tubules in proximal tubule cells [abstract].J. Am. Soc. Nephrol.(in press).
  33. Nourry, C., Grant, S.G., and Borg, J.P. (2003). PDZ domain proteins: plug and play!Sci. STKE2003, RE7. · DOI
  34. Nykjaer, A., Dragun, D., Walther, D., Vorum, H., Jacobsen, C., Herz, J., Melsen, F., Christensen, E.I., and Willnow, T.E. (1999). An endocytic pathway essential for renal uptake and activation of the steroid 25-(OH) vitamin D3.Cell96, 507-515. · DOI
  35. Oleinikov, A.V., Zhao, J., and Makker, S.P. (2000). Cytosolic adaptor protein Dab2 is an intracellular ligand of endocytic receptor gp600/megalin.Biochem. J.347, 613-621. · DOI · Paper page
  36. Orlando, R.A., Rader, K., Authier, F., Yamazaki, H., Posner, B.I., Bergeron, J.J., and Farquhar, M.G. (1998). Megalin is an endocytic receptor for insulin.J. Am. Soc. Nephrol.9, 1759-1766. · DOI
  37. Patrie, K.M., Drescher, A.J., Goyal, M., Wiggins, R.C., and Margolis, B. (2001). The membrane-associated guanylate kinase protein MAGI-1 binds megalin and is present in glomerular podocytes.J. Am. Soc. Nephrol.12, 667-677. · DOI
  38. Petersen, H.H., Hilpert, J., Militz, D., Zandler, V., Jacobsen, C., Roebroek, A.J., and Willnow, T.E. (2003). Functional interaction of megalin with the megalin-binding protein (MegBP), a novel tetratrico peptide repeat-containing adaptor molecule.J. Cell Sci.116, 453-461. · DOI
  39. Prekeris, R., Klumperman, J., Chen, Y.A., and Scheller, R.H. (1998). Syntaxin 13 mediates cycling of plasma membrane proteins via tubulovesicular recycling endosomes.J. Cell Biol.143, 957-971. · DOI · Paper page
  40. Rader, K., Orlando, R.A., Lou, X., and Farquhar, M.G. (2000). Characterization of ANKRA, a novel ankyrin repeat protein that interacts with the cytoplasmic domain of megalin.J. Am. Soc. Nephrol.11, 2167-2178. · DOI
  41. Sachse, M., Ramm, G., Strous, G., and Klumperman, J. (2002). Endosomes: multipurpose designs for integrating housekeeping and specialized tasks. Histochem.Cell Biol.117, 91-104. · DOI
  42. Saito, A., Pietromonaco, S., Loo, A.K., and Farquhar, M.G. (1994). Complete cloning and sequencing of rat gp330/“megalin,” a distinctive member of the low density lipoprotein receptor gene family.Proc. Natl. Acad. Sci. USA91, 9725-9729. · DOI
  43. Sonnichsen, B., De Renzis, S., Nielsen, E., Rietdorf, J., and Zerial, M. (2000). Distinct membrane domains on endosomes in the recycling pathway visualized by multicolor imaging of Rab4, Rab5, and Rab11.J. Cell Biol.149, 901-914. · DOI · Paper page
  44. Takeda, T., McQuistan, T., Orlando, R.A., and Farquhar, M.G. (2001). Loss of glomerular foot processes is associated with uncoupling of podocalyxin from the actin cytoskeleton.J. Clin. Investig.108, 289-301. · DOI
  45. Takeda, T., Yamazaki, H., and Farquhar, M.G. (2003). Identification of an Apical Sorting Determinant in the Cytoplasmic Tail of Megalin.Am. J. Physiol.284, C1105-C1113. · DOI
  46. Trischler, M., Stoorvogel, W., and Ullrich, O. (1999). Biochemical analysis of distinct Rab5- and Rab11-positive endosomes along the transferrin pathway.J. Cell Sci.112, 4773-4783. · DOI · Paper page
  47. Ullrich, O., Reinsch, S., Urbe, S., Zerial, M., and Parton, R.G. (1996). Rab11 regulates recycling through the pericentriolar recycling endosome.J. Cell Biol.135, 913-924. · DOI · Paper page
  48. Velasco, A., Hendricks, L., Moremen, K.W., Tulsiani, D.R., Touster, O., and Farquhar, M.G. (1993). Cell type-dependent variations in the subcellular distribution of alpha-mannosidase I and II.J. Cell Biol.122, 39-51. · DOI
  49. Willnow, T.E., Hilpert, J., Armstrong, S.A., Rohlmann, A., Hammer, R.E., Burns, D.K., and Herz, J. (1996). Defective forebrain development in mice lacking gp330/megalin.Proc. Natl. Acad. Sci. USA93, 8460-8464. · DOI
  50. Yamashiro, D.J., Tycko, B., Fluss, S.R., and Maxfield, F.R. (1984). Segregation of transferrin to a mildly acidic (pH 6.5) para-Golgi compartment in the recycling pathway.Cell37, 789-800. · DOI
  51. Yamazaki, H., Ullrich, R., Exner, M., Saito, A., Orlando, R.A., Kerjaschki, D., and Farquhar, M.G. (1998). All four putative ligand-binding domains in megalin contain pathogenic epitopes capable of inducing passive Heymann nephritis.J. Am. Soc. Nephrol.9, 1638-1644. · DOI
  52. Yan, K.S., Kuti, M., and Zhou, M.M. (2002). PTB or not PTB – that is the question.FEBS Lett513, 67-70. · DOI
  53. Zheng, G., Bachinsky, D.R., Stamenkovic, I., Strickland, D.K., Brown, D., Andres, G., and McCluskey, R.T. (1994). Organ distribution in rats of two members of the low-density lipoprotein receptor gene family, gp330 and LRP/alpha 2MR, and the receptor-associated protein (RAP).J. Histochem. Cytochem.42, 531-542. · DOI

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Metadata

Authors
Nagai, M., Meerloo, T., Takeda, T., & Farquhar, M. G.
Affiliations
Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, California 92093
Venue
Molecular Biology of the Cell
Publisher
American Society for Cell Biology (ASCB)
Published
2003-12
Volume
14
Issue
12
Pages
4984-4996
ISSN
  • 1059-1524
  • 1939-4586
DOI
10.1091/mbc.e03-06-0385
Cited by
91
References
2
Language
en

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