N-Glycans Mediate the Apical Sorting of a GPI-anchored, Raft-associated Protein in Madin-Darby Canine Kidney Cells

Correspondence to: Kai Simons, European Molecular Biology Laboratory (EMBL), Cell Biology and Biophysics Programme, Postfach 102209, Meyerhofstrasse 1, D-69012 Heidelberg, Germany., Simons{at}EMBL-Heidelberg.de (E-mail), 49-6221-387-334 (phone), 49-6221-387-512 (fax)

Glycosyl-phosphatidylinositol (GPI)- anchored proteins are preferentially transported to the apical cell surface of polarized Madin-Darby canine kidney (MDCK) cells. It has been assumed that the GPI anchor itself acts as an apical determinant by its interaction with sphingolipid-cholesterol rafts. We modified the rat growth hormone (rGH), an unglycosylated, unpolarized secreted protein, into a GPI-anchored protein and analyzed its surface delivery in polarized MDCK cells. The addition of a GPI anchor to rGH did not lead to an increase in apical delivery of the protein. However, addition of N-glycans to GPI-anchored rGH resulted in predominant apical delivery, suggesting that N-glycans act as apical sorting signals on GPI-anchored proteins as they do on transmembrane and secretory proteins. In contrast to the GPI-anchored rGH, a transmembrane form of rGH which was not raft-associated accumulated intracellularly. Addition of N-glycans to this chimeric protein prevented intracellular accumulation and led to apical delivery.

Key Words: lipid rafts, N-glycans, GPI-anchored proteins, Madin-Darby canine kidney cells, sorting

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Pocard, T., Le Bivic, A., Galli, T., Zurzolo, C. (2007). Distinct v-SNAREs regulate direct and indirect apical delivery in polarized epithelial cells. J. Cell Sci. 120: 3309-3320 [Abstract] [Full Text]  
• Chmelar, R. S., Nathanson, N. M. (2006). Identification of a Novel Apical Sorting Motif and Mechanism of Targeting of the M2 Muscarinic Acetylcholine Receptor. J. Biol. Chem. 281: 35381-35396 [Abstract] [Full Text]  
• Nakagawa, T., Uozumi, N., Nakano, M., Mizuno-Horikawa, Y., Okuyama, N., Taguchi, T., Gu, J., Kondo, A., Taniguchi, N., Miyoshi, E. (2006). Fucosylation of N-Glycans Regulates the Secretion of Hepatic Glycoproteins into Bile Ducts. J. Biol. Chem. 281: 29797-29806 [Abstract] [Full Text]  
• Cabrera, J. R., Sanchez-Pulido, L., Rojas, A. M., Valencia, A., Manes, S., Naranjo, J. R., Mellstrom, B. (2006). Gas1 Is Related to the Glial Cell-derived Neurotrophic Factor Family Receptors {alpha} and Regulates Ret Signaling. J. Biol. Chem. 281: 14330-14339 [Abstract] [Full Text]  
• Schuck, S., Simons, K. (2006). Controversy fuels trafficking of GPI-anchored proteins.. J. Cell Biol. 172: 963-965 [Abstract] [Full Text]  
• Smith, D. C., Sillence, D. J., Falguieres, T., Jarvis, R. M., Johannes, L., Lord, J. M., Platt, F. M., Roberts, L. M. (2006). The Association of Shiga-like Toxin with Detergent-resistant Membranes Is Modulated by Glucosylceramide and Is an Essential Requirement in the Endoplasmic Reticulum for a Cytotoxic Effect. Mol. Biol. Cell 17: 1375-1387 [Abstract] [Full Text]  
• Potter, B. A., Hughey, R. P., Weisz, O. A. (2006). Role of N- and O-glycans in polarized biosynthetic sorting. Am. J. Physiol. Cell Physiol. 290: C1-C10 [Abstract] [Full Text]  
• Rai, T., Sasaki, S., Uchida, S. (2006). Polarized trafficking of the aquaporin-3 water channel is mediated by an NH2-terminal sorting signal. Am. J. Physiol. Cell Physiol. 290: C298-C304 [Abstract] [Full Text]  
• Tveit, H., Dick, G., Skibeli, V., Prydz, K. (2005). A Proteoglycan Undergoes Different Modifications en Route to the Apical and Basolateral Surfaces of Madin-Darby Canine Kidney Cells. J. Biol. Chem. 280: 29596-29603 [Abstract] [Full Text]  
• Coudroy, G., Gburek, J., Kozyraki, R., Madsen, M., Trugnan, G., Moestrup, S. K., Verroust, P. J., Maurice, M. (2005). Contribution of Cubilin and Amnionless to Processing and Membrane Targeting of Cubilin-Amnionless Complex. J. Am. Soc. Nephrol. 16: 2330-2337 [Abstract] [Full Text]  
• Devuyst, O., Dahan, K., Pirson, Y. (2005). Tamm-Horsfall protein or uromodulin: new ideas about an old molecule. Nephrol Dial Transplant 20: 1290-1294 [Full Text]  
• Delacour, D., Gouyer, V., Zanetta, J.-P., Drobecq, H., Leteurtre, E., Grard, G., Moreau-Hannedouche, O., Maes, E., Pons, A., Andre, S., Le Bivic, A., Gabius, H. J., Manninen, A., Simons, K., Huet, G. (2005). Galectin-4 and sulfatides in apical membrane trafficking in enterocyte-like cells. J. Cell Biol. 169: 491-501 [Abstract] [Full Text]  
• Vigdorovich, V., Strong, R. K., Miller, A. D. (2005). Expression and Characterization of a Soluble, Active Form of the Jaagsiekte Sheep Retrovirus Receptor, Hyal2. J. Virol. 79: 79-86 [Abstract] [Full Text]  
• Schuck, S., Simons, K. (2004). Polarized sorting in epithelial cells: raft clustering and the biogenesis of the apical membrane. J. Cell Sci. 117: 5955-5964 [Abstract] [Full Text]  
• Paladino, S., Sarnataro, D., Pillich, R., Tivodar, S., Nitsch, L., Zurzolo, C. (2004). Protein oligomerization modulates raft partitioning and apical sorting of GPI-anchored proteins. J. Cell Biol. 167: 699-709 [Abstract] [Full Text]  
• Pang, S., Urquhart, P., Hooper, N. M. (2004). N-Glycans, not the GPI anchor, mediate the apical targeting of a naturally glycosylated, GPI-anchored protein in polarised epithelial cells. J. Cell Sci. 117: 5079-5086 [Abstract] [Full Text]  
• Regeer, R. R., Markovich, D. (2004). A dileucine motif targets the sulfate anion transporter sat-1 to the basolateral membrane in renal cell lines. Am. J. Physiol. Cell Physiol. 287: C365-C372 [Abstract] [Full Text]  
• Paquet, S., Sabuncu, E., Delaunay, J.-L., Laude, H., Vilette, D. (2004). Prion Infection of Epithelial Rov Cells Is a Polarized Event. J. Virol. 78: 7148-7152 [Abstract] [Full Text]  
• Brown, A., Muth, T., Caplan, M. (2004). The COOH-terminal tail of the GAT-2 GABA transporter contains a novel motif that plays a role in basolateral targeting. Am. J. Physiol. Cell Physiol. 286: C1071-C1077 [Abstract] [Full Text]  
• Proszynski, T. J., Simons, K., Bagnat, M. (2004). O-Glycosylation as a Sorting Determinant for Cell Surface Delivery in Yeast. Mol. Biol. Cell 15: 1533-1543 [Abstract] [Full Text]  
• Burgos, P. V., Klattenhoff, C., de la Fuente, E., Rigotti, A., Gonzalez, A. (2004). Cholesterol depletion induces PKA-mediated basolateral-to-apical transcytosis of the scavenger receptor class B type I in MDCK cells. Proc. Natl. Acad. Sci. USA 101: 3845-3850 [Abstract] [Full Text]  
• Toye, A. M., Banting, G., Tanner, M. J. A. (2004). Regions of human kidney anion exchanger 1 (kAE1) required for basolateral targeting of kAE1 in polarised kidney cells: mis-targeting explains dominant renal tubular acidosis (dRTA). J. Cell Sci. 117: 1399-1410 [Abstract] [Full Text]  
• Brady, J. D., Rich, T. C., Le, X., Stafford, K., Fowler, C. J., Lynch, L., Karpen, J. W., Brown, R. L., Martens, J. R. (2004). Functional Role of Lipid Raft Microdomains in Cyclic Nucleotide-Gated Channel Activation. Mol. Pharmacol. 65: 503-511 [Abstract] [Full Text]  
• Potter, B. A., Ihrke, G., Bruns, J. R., Weixel, K. M., Weisz, O. A. (2004). Specific N-Glycans Direct Apical Delivery of Transmembrane, but Not Soluble or Glycosylphosphatidylinositol-anchored Forms of Endolyn in Madin-Darby Canine Kidney Cells. Mol. Biol. Cell 15: 1407-1416 [Abstract] [Full Text]  
• Popik, W., Alce, T. M. (2004). CD4 Receptor Localized to Non-raft Membrane Microdomains Supports HIV-1 Entry: IDENTIFICATION OF A NOVEL RAFT LOCALIZATION MARKER IN CD4. J. Biol. Chem. 279: 704-712 [Abstract] [Full Text]  
• Bonnon, C., Goutebroze, L., Denisenko-Nehrbass, N., Girault, J.-A., Faivre-Sarrailh, C. (2003). The Paranodal Complex of F3/Contactin and Caspr/Paranodin Traffics to the Cell Surface via a Non-conventional Pathway. J. Biol. Chem. 278: 48339-48347 [Abstract] [Full Text]  
• Delacour, D., Gouyer, V., Leteurtre, E., Ait-Slimane, T., Drobecq, H., Lenoir, C., Moreau-Hannedouche, O., Trugnan, G., Huet, G. (2003). 1-Benzyl-2-acetamido-2-deoxy-{alpha}-D-galactopyranoside Blocks the Apical Biosynthetic Pathway in Polarized HT-29 Cells. J. Biol. Chem. 278: 37799-37809 [Abstract] [Full Text]  
• Zhu, A. J., Zheng, L., Suyama, K., Scott, M. P. (2003). Altered localization of Drosophila Smoothened protein activates Hedgehog signal transduction. Genes Dev. 17: 1240-1252 [Abstract] [Full Text]  
• Hoekstra, D., Maier, O., van der Wouden, J. M., Slimane, T. A., van IJzendoorn, S. C. D. (2003). Membrane dynamics and cell polarity: the role of sphingolipids. J. Lipid Res. 44: 869-877 [Abstract] [Full Text]  
• Caplan, M. J. (2003). How megalin finds its way: identification of a novel apical sorting motif. Focus on "Identification of an apical sorting determinant in the cytoplasmic tail of megalin". Am. J. Physiol. Cell Physiol. 284: C1101-C1104 [Full Text]  
• Holm, K., Weclewicz, K., Hewson, R., Suomalainen, M. (2003). Human Immunodeficiency Virus Type 1 Assembly and Lipid Rafts: Pr55gag Associates with Membrane Domains That Are Largely Resistant to Brij98 but Sensitive to Triton X-100. J. Virol. 77: 4805-4817 [Abstract] [Full Text]  
• Leteurtre, E., Gouyer, V., Delacour, D., Hemon, B., Pons, A., Richet, C., Zanetta, J.-P., Huet, G. (2003). Induction of a Storage Phenotype and Abnormal Intracellular Localization of Apical Glycoproteins Are Two Independent Responses to GalNAc{alpha}-O-bn. J. Histochem. Cytochem. 51: 349-361 [Abstract] [Full Text]  
• Abrami, L., Fivaz, M., Glauser, P.-E., Sugimoto, N., Zurzolo, C., van der Goot, F. G. (2003). Sensitivity of Polarized Epithelial Cells to the Pore-Forming Toxin Aerolysin. Infect. Immun. 71: 739-746 [Abstract] [Full Text]  
• Maier, O., Hoekstra, D. (2003). Trans-Golgi Network and Subapical Compartment of HepG2 Cells Display Different Properties in Sorting and Exiting of Sphingolipids. J. Biol. Chem. 278: 164-173 [Abstract] [Full Text]  
• Zhang, H., Martin-Deleon, P. A. (2003). Mouse Epididymal Spam1 (PH-20) Is Released in the Luminal Fluid With its Lipid Anchor. J Androl 24: 51-58 [Abstract] [Full Text]  
• Tabuchi, M., Tanaka, N., Nishida-Kitayama, J., Ohno, H., Kishi, F. (2002). Alternative Splicing Regulates the Subcellular Localization of Divalent Metal Transporter 1 Isoforms. Mol. Biol. Cell 13: 4371-4387 [Abstract] [Full Text]  
• Borner, G. H.H., Sherrier, D. J., Stevens, T. J., Arkin, I. T., Dupree, P. (2002). Prediction of Glycosylphosphatidylinositol-Anchored Proteins in Arabidopsis. A Genomic Analysis. Plant Physiol. 129: 486-499 [Abstract] [Full Text]  
• Bulbarelli, A., Sprocati, T., Barberi, M., Pedrazzini, E., Borgese, N. (2002). Trafficking of tail-anchored proteins: transport from the endoplasmic reticulum to the plasma membrane and sorting between surface domains in polarised epithelial cells. J. Cell Sci. 115: 1689-1702 [Abstract] [Full Text]  
• Stallcup, W. B., Dahlin-Huppe, K. (2002). Chondroitin sulfate and cytoplasmic domain-dependent membrane targeting of the NG2 proteoglycan promotes retraction fiber formation and cell polarization. J. Cell Sci. 114: 2315-2325 [Abstract] [Full Text]  
• Spodsberg, N., Alfalah, M., Naim, H. Y. (2001). Characteristics and Structural Requirements of Apical Sorting of the Rat Growth Hormone through the O-Glycosylated Stalk Region of Intestinal Sucrase-isomaltase. J. Biol. Chem. 276: 46597-46604 [Abstract] [Full Text]  
• Holthuis, J. C. M., Pomorski, T., Raggers, R. J., Sprong, H., Van Meer, G. (2001). The Organizing Potential of Sphingolipids in Intracellular Membrane Transport. Physiol. Rev. 81: 1689-1723 [Abstract] [Full Text]  
• Zhang, Z., Austin, S. C., Smyth, E. M. (2001). Glycosylation of the Human Prostacyclin Receptor: Role in Ligand Binding and Signal Transduction. Mol. Pharmacol. 60: 480-487 [Abstract] [Full Text]  
• Pickl, W. F., Pimentel-Muinos, F. X., Seed, B. (2001). Lipid Rafts and Pseudotyping. J. Virol. 75: 7175-7183 [Abstract] [Full Text]  
• Falguieres, T., Mallard, F., Baron, C., Hanau, D., Lingwood, C., Goud, B., Salamero, J., Johannes, L. (2001). Targeting of Shiga Toxin B-Subunit to Retrograde Transport Route in Association with Detergent-resistant Membranes. Mol. Biol. Cell 12: 2453-2468 [Abstract] [Full Text]  
• Nichols, B. J., Kenworthy, A. K., Polishchuk, R. S., Lodge, R., Roberts, T. H., Hirschberg, K., Phair, R. D., Lippincott-Schwartz, J. (2001). Rapid Cycling of Lipid Raft Markers between the Cell Surface and Golgi Complex. J. Cell Biol. 153: 529-542 [Abstract] [Full Text]  
• Rai, S. K., Duh, F.-M., Vigdorovich, V., Danilkovitch-Miagkova, A., Lerman, M. I., Miller, A. D. (2001). Candidate tumor suppressor HYAL2 is a glycosylphosphatidylinositol (GPI)-anchored cell-surface receptor for jaagsiekte sheep retrovirus, the envelope protein of which mediates oncogenic transformation. Proc. Natl. Acad. Sci. USA 98: 4443-4448 [Abstract] [Full Text]  
• Gouyer, V, Leteurtre, E, Delmotte, P, Steelant, W., Krzewinski-Recchi, M., Zanetta, J., Lesuffleur, T, Trugnan, G, Delannoy, P, Huet, G (2001). Differential effect of GalNAc(&agr;)-O-bn on intracellular trafficking in enterocytic HT-29 and Caco-2 cells: correlation with the glycosyltransferase expression pattern. J. Cell Sci. 114: 1455-1471 [Abstract]  
• Sproul, T. W., Malapati, S., Kim, J., Pierce, S. K. (2000). Cutting Edge: B Cell Antigen Receptor Signaling Occurs Outside Lipid Rafts in Immature B Cells. J. Immunol. 165: 6020-6023 [Abstract] [Full Text]  
• Grimmer, S., Iversen, T.-G., van Deurs, B., Sandvig, K. (2000). Endosome to Golgi Transport of Ricin Is Regulated by Cholesterol. Mol. Biol. Cell 11: 4205-4216 [Abstract] [Full Text]  
• Bravo-Zehnder, M., Orio, P., Norambuena, A., Wallner, M., Meera, P., Toro, L., Latorre, R., González, A. (2000). Apical sorting of a voltage- and Ca2+-activated K+ channel alpha -subunit in Madin-Darby canine kidney cells is independent of N-glycosylation. Proc. Natl. Acad. Sci. USA 10.1073/pnas.240455697v1 [Abstract] [Full Text]  
• Gagescu, R., Demaurex, N., Parton, R. G., Hunziker, W., Huber, L. A., Gruenberg, J. (2000). The Recycling Endosome of Madin-Darby Canine Kidney Cells Is a Mildly Acidic Compartment Rich in Raft Components. Mol. Biol. Cell 11: 2775-2791 [Abstract] [Full Text]  
• Barman, S., Nayak, D. P. (2000). Analysis of the Transmembrane Domain of Influenza Virus Neuraminidase, a Type II Transmembrane Glycoprotein, for Apical Sorting and Raft Association. J. Virol. 74: 6538-6545 [Abstract] [Full Text]  
• Chen, C., Colley, K. J. (2000). Minimal structural and glycosylation requirements for ST6Gal I activity and trafficking. Glycobiology 10: 531-583 [Abstract] [Full Text]  
• Stevens, A. L., Breton, S., Gustafson, C. E., Bouley, R., Nelson, R. D., Kohan, D. E., Brown, D. (2000). Aquaporin 2 is a vasopressin-independent, constitutive apical membrane protein in rat vas deferens. Am. J. Physiol. Cell Physiol. 278: C791-C802 [Abstract] [Full Text]  
• Verkade, P., Harder, T., Lafont, F., Simons, K. (2000). Induction of Caveolae in the Apical Plasma Membrane of Madin-Darby Canine Kidney Cells. J. Cell Biol. 148: 727-740 [Abstract] [Full Text]  
• Brown, D. (2000). Targeting of membrane transporters in renal epithelia: when cell biology meets physiology. Am. J. Physiol. Renal Physiol. 278: F192-F201 [Abstract] [Full Text]  
• Lipardi, C., Nitsch, L., Zurzolo, C. (2000). Detergent-insoluble GPI-anchored Proteins Are Apically Sorted in Fischer Rat Thyroid Cells, but Interference with Cholesterol or Sphingolipids Differentially Affects Detergent Insolubility and Apical Sorting. Mol. Biol. Cell 11: 531-542 [Abstract] [Full Text]  
• Meerson, N., Bello, V, Delaunay, J., Slimane, T., Delautier, D, Lenoir, C, Trugnan, G, Maurice, M (2000). Intracellular traffic of the ecto-nucleotide pyrophosphatase/phosphodiesterase NPP3 to the apical plasma membrane of MDCK and Caco-2 cells: apical targeting occurs in the absence of N-glycosylation. J. Cell Sci. 113: 4193-4202 [Abstract]  
• Weise, F, Stierhof, Y., Kuhn, C, Wiese, M, Overath, P (2000). Distribution of GPI-anchored proteins in the protozoan parasite Leishmania, based on an improved ultrastructural description using high-pressure frozen cells. J. Cell Sci. 113: 4587-4603 [Abstract]  
• Lecat, S, Verkade, P, Thiele, C, Fiedler, K, Simons, K, Lafont, F (2000). Different properties of two isoforms of annexin XIII in MDCK cells. J. Cell Sci. 113: 2607-2618 [Abstract]  
• Prydz, K, Dalen, K. (2000). Synthesis and sorting of proteoglycans. J. Cell Sci. 113: 193-205 [Abstract]  
• Martin-Belmonte, F., Alonso, M. A., Zhang, X., Arvan, P. (2000). Thyroglobulin Is Selected as Luminal Protein Cargo for Apical Transport via Detergent-resistant Membranes in Epithelial Cells. J. Biol. Chem. 275: 41074-41081 [Abstract] [Full Text]  
• Scott, R. P., Ibanez, C. F. (2001). Determinants of Ligand Binding Specificity in the Glial Cell Line-derived Neurotrophic Factor Family Receptor alpha s. J. Biol. Chem. 276: 1450-1458 [Abstract] [Full Text]  
• Wehrle-Haller, B., Imhof, B. A. (2001). Stem Cell Factor Presentation to c-Kit. IDENTIFICATION OF A BASOLATERAL TARGETING DOMAIN. J. Biol. Chem. 276: 12667-12674 [Abstract] [Full Text]  
• Cohen, C. J., Gaetz, J., Ohman, T., Bergelson, J. M. (2001). Multiple Regions within the Coxsackievirus and Adenovirus Receptor Cytoplasmic Domain Are Required for Basolateral Sorting. J. Biol. Chem. 276: 25392-25398 [Abstract] [Full Text]  
• Yang, H., Reinherz, E. L. (2001). Dynamic Recruitment of Human CD2 into Lipid Rafts. LINKAGE TO T CELL SIGNAL TRANSDUCTION. J. Biol. Chem. 276: 18775-18785 [Abstract] [Full Text]  
• Miranda, K. C., Khromykh, T., Christy, P., Le, T. L., Gottardi, C. J., Yap, A. S., Stow, J. L., Teasdale, R. D. (2001). A Dileucine Motif Targets E-cadherin to the Basolateral Cell Surface in Madin-Darby Canine Kidney and LLC-PK1 Epithelial Cells. J. Biol. Chem. 276: 22565-22572 [Abstract] [Full Text]  
• Martin-Belmonte, F., Arvan, P., Alonso, M. A. (2001). MAL Mediates Apical Transport of Secretory Proteins in Polarized Epithelial Madin-Darby Canine Kidney Cells. J. Biol. Chem. 276: 49337-49342 [Abstract] [Full Text]  
• Brown, D. A., London, E. (2000). Structure and Function of Sphingolipid- and Cholesterol-rich Membrane Rafts. J. Biol. Chem. 275: 17221-17224 [Full Text]  
• Bravo-Zehnder, M., Orio, P., Norambuena, A., Wallner, M., Meera, P., Toro, L., Latorre, R., Gonzalez, A. (2000). Apical sorting of a voltage- and Ca2+-activated K+ channel alpha -subunit in Madin-Darby canine kidney cells is independent of N-glycosylation. Proc. Natl. Acad. Sci. USA 97: 13114-13119 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents