Home LiteratureArticle Details
PMID: 18971212 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Review

Role of N-glycosylation in trafficking of apical membrane proteins in epithelia.

American journal of physiology. Renal physiology ·Vol. 296 ·No. 3 ·2009-03-00 ·Pages F459-69

Vagin O, Kraut JA, Sachs G

Abstract

Polarized distribution of plasma membrane transporters and receptors in epithelia is essential for vectorial functions of epithelia. This polarity is maintained by sorting of membrane proteins into apical or basolateral transport containers in the trans-Golgi network and/or endosomes followed by their delivery to the appropriate plasma membrane domains. Sorting depends on the recognition of sorting signals in proteins by specific sorting machinery. In the present review, we summarize experimental evidence for and against the hypothesis that N-glycans attached to the membrane proteins can act as apical sorting signals. Furthermore, we discuss the roles of N-glycans in the apical sorting event per se and their contribution to folding and quality control of glycoproteins in the endoplasmic reticulum or retention of glycoproteins in the plasma membrane. Finally, we review existing hypotheses on the mechanism of apical sorting and discuss the potential roles of the lectins, VIP36 and galectin-3, as putative apical sorting receptors.

MeSH Terms
Endoplasmic Reticulum/metabolism Epithelial Cells/metabolism Glycoproteins/metabolism Glycosylation Golgi Apparatus/metabolism Membrane Microdomains/metabolism Membrane Proteins/metabolism Protein Folding Protein Sorting Signals Protein Stability
Chemicals
Glycoproteins Membrane Proteins Protein Sorting Signals
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Vagin Olga
Department of Physiology, David Geffen School of Medicine at University of California, Bldg. 113, Rm. 324, 11301 Wilshire Blvd., Los Angeles, California 90073, USA. olgav@ucla.edu
Kraut Jeffrey A
Sachs George
References (94)
94 references, click to expand
  1. Regulation of cytokine receptors by Golgi N-glycan processing and endocytosis.
    Science. 2004 Oct 1;306(5693):120-4 PMID: 15459394
  2. Contribution of oligosaccharides to protection of the H,K-ATPase beta-subunit against trypsinolysis.
    Electrophoresis. 2004 Aug;25(15):2586-92 PMID: 15300779
  3. Sorting of rat SPNT in renal epithelium is independent of N-glycosylation.
    Pharm Res. 2003 Feb;20(2):319-23 PMID: 12636174
  4. Structural requirements for basolateral sorting of the human transferrin receptor in the biosynthetic and endocytic pathways of Madin-Darby canine kidney cells.
    J Cell Biol. 1997 Jun 16;137(6):1255-64 PMID: 9182660
  5. Clusters, bundles, arrays and lattices: novel mechanisms for lectin-saccharide-mediated cellular interactions.
    Curr Opin Struct Biol. 2002 Oct;12(5):616-23 PMID: 12464313
  6. Oligomerization is a specific requirement for apical sorting of glycosyl-phosphatidylinositol-anchored proteins but not for non-raft-associated apical proteins.
    Traffic. 2007 Mar;8(3):251-8 PMID: 17233758
  7. In and out of the ER: protein folding, quality control, degradation, and related human diseases.
    Physiol Rev. 2007 Oct;87(4):1377-408 PMID: 17928587
  8. N-glycan processing in ER quality control.
    J Cell Sci. 2006 Nov 1;119(Pt 21):4373-80 PMID: 17074831
  9. Asparagine-linked oligosaccharides protect Lamp-1 and Lamp-2 from intracellular proteolysis.
    J Biol Chem. 1999 Oct 22;274(43):31039-46 PMID: 10521503
  10. Galectin-4 and small intestinal brush border enzymes form clusters.
    Mol Biol Cell. 1997 Nov;8(11):2241-51 PMID: 9362066
  11. The O-glycosylated stalk domain is required for apical sorting of neurotrophin receptors in polarized MDCK cells.
    J Cell Biol. 1997 Nov 17;139(4):929-40 PMID: 9362511
  12. Polarized epithelial membrane traffic: conservation and plasticity.
    Nat Cell Biol. 2003 Apr;5(4):287-93 PMID: 12669082
  13. Effects of glycosylation on peptide conformation: a synergistic experimental and computational study.
    J Am Chem Soc. 2004 Jul 14;126(27):8421-5 PMID: 15237998
  14. Identification of glycosylated marker proteins of epithelial polarity in MDCK cells by homology driven proteomics.
    BMC Biochem. 2006;7:8 PMID: 16533391
  15. Apical sorting of bovine enteropeptidase does not involve detergent-resistant association with sphingolipid-cholesterol rafts.
    J Biol Chem. 1999 Jan 15;274(3):1596-605 PMID: 9880538
  16. Organization of vesicular trafficking in epithelia.
    Nat Rev Mol Cell Biol. 2005 Mar;6(3):233-47 PMID: 15738988
  17. Lipid rafts, detergent-resistant membranes, and raft targeting signals.
    Physiology (Bethesda). 2006 Dec;21:430-9 PMID: 17119156
  18. Transport protein trafficking in polarized cells.
    Annu Rev Cell Dev Biol. 2003;19:333-66 PMID: 14570573
  19. Roles of N-linked glycans in the endoplasmic reticulum.
    Annu Rev Biochem. 2004;73:1019-49 PMID: 15189166
  20. 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. 2004 Mar;15(3):1407-16 PMID: 14699065
  21. Carbohydrate-mediated Golgi to cell surface transport and apical targeting of membrane proteins.
    EMBO J. 1998 Apr 1;17(7):1919-29 PMID: 9524115
  22. Two N-linked glycans are required to maintain the transport activity of the bile salt export pump (ABCB11) in MDCK II cells.
    Am J Physiol Gastrointest Liver Physiol. 2007 Mar;292(3):G818-28 PMID: 17082223
  23. Junctional complexes in various epithelia.
    J Cell Biol. 1963 May;17:375-412 PMID: 13944428
  24. Gender-related association of serum uric acid and left ventricular hypertrophy in hypertension.
    Circ J. 2006 Jul;70(7):885-8 PMID: 16799243
  25. The epithelial-specific adaptor AP1B mediates post-endocytic recycling to the basolateral membrane.
    Nat Cell Biol. 2002 Aug;4(8):605-9 PMID: 12105417
  26. Localization of VIP36 in the post-Golgi secretory pathway also of rat parotid acinar cells.
    J Histochem Cytochem. 2003 Aug;51(8):1057-63 PMID: 12871987
  27. Plasma membrane domain organization regulates EGFR signaling in tumor cells.
    J Cell Biol. 2007 Oct 22;179(2):341-56 PMID: 17938246
  28. Recombinant addition of N-glycosylation sites to the basolateral Na,K-ATPase beta1 subunit results in its clustering in caveolae and apical sorting in HGT-1 cells.
    J Biol Chem. 2005 Dec 30;280(52):43159-67 PMID: 16230337
  29. Identification of a novel apical sorting motif and mechanism of targeting of the M2 muscarinic acetylcholine receptor.
    J Biol Chem. 2006 Nov 17;281(46):35381-96 PMID: 16968700
  30. Epithelial trafficking: new routes to familiar places.
    Curr Opin Cell Biol. 2004 Aug;16(4):436-42 PMID: 15261677
  31. A chaperone with a sweet tooth.
    Curr Biol. 1993 Dec 1;3(12):884-6 PMID: 15335825
  32. Model systems, lipid rafts, and cell membranes.
    Annu Rev Biophys Biomol Struct. 2004;33:269-95 PMID: 15139814
  33. The functional role of beta subunits in oligomeric P-type ATPases.
    J Bioenerg Biomembr. 2001 Oct;33(5):425-38 PMID: 11762918
  34. The H,K-ATPase beta subunit as a model to study the role of N-glycosylation in membrane trafficking and apical sorting.
    J Biol Chem. 2004 Sep 10;279(37):39026-34 PMID: 15247221
  35. Role of glycosylation and disulfide bond formation in the beta subunit in the folding and functional expression of Na,K-ATPase.
    J Biol Chem. 1997 Apr 11;272(15):10318-26 PMID: 9092584
  36. Folding of VSV G protein: sequential interaction with BiP and calnexin.
    Science. 1994 Oct 21;266(5184):456-8 PMID: 7939687
  37. N-glycans mediate apical recycling of the sialomucin endolyn in polarized MDCK cells.
    Traffic. 2006 Feb;7(2):146-54 PMID: 16420523
  38. N-glycans as apical targeting signals in polarized epithelial cells.
    Biochem Soc Symp. 2005;(72):39-45 PMID: 15649128
  39. Trafficking of lysosomal enzymes.
    FASEB J. 1987 Dec;1(6):462-8 PMID: 3315809
  40. Interaction of influenza virus haemagglutinin with sphingolipid-cholesterol membrane domains via its transmembrane domain.
    EMBO J. 1997 Sep 15;16(18):5501-8 PMID: 9312009
  41. Temporal association of the N- and O-linked glycosylation events and their implication in the polarized sorting of intestinal brush border sucrase-isomaltase, aminopeptidase N, and dipeptidyl peptidase IV.
    J Biol Chem. 1999 Jun 18;274(25):17961-7 PMID: 10364244
  42. Differential extractability of influenza virus hemagglutinin during intracellular transport in polarized epithelial cells and nonpolar fibroblasts.
    J Cell Biol. 1989 Mar;108(3):821-32 PMID: 2522097
  43. Involvement of VIP36 in intracellular transport and secretion of glycoproteins in polarized Madin-Darby canine kidney (MDCK) cells.
    J Biol Chem. 2002 May 3;277(18):16332-9 PMID: 11872745
  44. Molecular determinants involved in the asymmetrical distribution of glycine transporters in polarized cells.
    Biochem Soc Trans. 2001 Nov;29(Pt 6):746-50 PMID: 11709068
  45. Galectin-4 and sulfatides in apical membrane trafficking in enterocyte-like cells.
    J Cell Biol. 2005 May 9;169(3):491-501 PMID: 15883199
  46. The number and location of glycans on influenza hemagglutinin determine folding and association with calnexin and calreticulin.
    J Cell Biol. 1997 Nov 3;139(3):613-23 PMID: 9348279
  47. Lectins and protein traffic early in the secretory pathway.
    Biochem Soc Symp. 2002;(69):73-82 PMID: 12655775
  48. Role of N- and O-glycans in polarized biosynthetic sorting.
    Am J Physiol Cell Physiol. 2006 Jan;290(1):C1-C10 PMID: 16338974
  49. Profile-based data base scanning for animal L-type lectins and characterization of VIPL, a novel VIP36-like endoplasmic reticulum protein.
    J Biol Chem. 2003 May 2;278(18):15886-96 PMID: 12609988
  50. Glycosylation of Eag1 (Kv10.1) potassium channels: intracellular trafficking and functional consequences.
    J Biol Chem. 2005 Aug 19;280(33):29506-12 PMID: 15964838
  51. A dileucine motif in its cytoplasmic domain directs beta-catenin-uncoupled E-cadherin to the lysosome.
    J Cell Sci. 2007 Dec 15;120(Pt 24):4395-406 PMID: 18057030
  52. PrP(C) association with lipid rafts in the early secretory pathway stabilizes its cellular conformation.
    Mol Biol Cell. 2004 Sep;15(9):4031-42 PMID: 15229281
  53. Functional rafts in cell membranes.
    Nature. 1997 Jun 5;387(6633):569-72 PMID: 9177342
  54. Statistical analysis of the protein environment of N-glycosylation sites: implications for occupancy, structure, and folding.
    Glycobiology. 2004 Feb;14(2):103-14 PMID: 14514716
  55. The role of N-glycans in the secretory pathway.
    Cell. 1995 May 5;81(3):309-12 PMID: 7736583
  56. Effect of N-linked glycosylation on glycopeptide and glycoprotein structure.
    Curr Opin Chem Biol. 1999 Dec;3(6):643-9 PMID: 10600722
  57. 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. 2002 Apr 15;115(Pt 8):1689-702 PMID: 11950887
  58. Dietary and genetic control of glucose transporter 2 glycosylation promotes insulin secretion in suppressing diabetes.
    Cell. 2005 Dec 29;123(7):1307-21 PMID: 16377570
  59. A novel clathrin adaptor complex mediates basolateral targeting in polarized epithelial cells.
    Cell. 1999 Oct 15;99(2):189-98 PMID: 10535737
  60. Complex N-glycans are the major ligands for galectin-1, -3, and -8 on Chinese hamster ovary cells.
    Glycobiology. 2006 Apr;16(4):305-17 PMID: 16319083
  61. Induction of caveolae in the apical plasma membrane of Madin-Darby canine kidney cells.
    J Cell Biol. 2000 Feb 21;148(4):727-39 PMID: 10684254
  62. Lipids as targeting signals: lipid rafts and intracellular trafficking.
    Traffic. 2004 Apr;5(4):247-54 PMID: 15030566
  63. Regulation of membrane trafficking in polarized epithelial cells.
    Curr Opin Cell Biol. 2008 Apr;20(2):208-13 PMID: 18282697
  64. Site-specific glycosylation analysis of the bovine lysosomal alpha-mannosidase.
    Glycobiology. 2006 May;16(5):440-61 PMID: 16449350
  65. Polarized biosynthetic traffic in renal epithelial cells: sorting, sorting, everywhere.
    Am J Physiol Renal Physiol. 2006 Oct;291(4):F707-13 PMID: 16788143
  66. Polarized sorting in epithelial cells: raft clustering and the biogenesis of the apical membrane.
    J Cell Sci. 2004 Dec 1;117(Pt 25):5955-64 PMID: 15564373
  67. Glycosylation in cellular mechanisms of health and disease.
    Cell. 2006 Sep 8;126(5):855-67 PMID: 16959566
  68. Mannose 6-phosphate receptors: new twists in the tale.
    Nat Rev Mol Cell Biol. 2003 Mar;4(3):202-12 PMID: 12612639
  69. N-Glycans mediate the apical sorting of a GPI-anchored, raft-associated protein in Madin-Darby canine kidney cells.
    J Cell Biol. 1999 Jul 26;146(2):313-20 PMID: 10427087
  70. Molecular basis of sugar recognition by the human L-type lectins ERGIC-53, VIPL, and VIP36.
    J Biol Chem. 2008 Jan 25;283(4):1857-61 PMID: 18025080
  71. A dileucine motif targets E-cadherin to the basolateral cell surface in Madin-Darby canine kidney and LLC-PK1 epithelial cells.
    J Biol Chem. 2001 Jun 22;276(25):22565-72 PMID: 11312273
  72. Analysis of the transmembrane domain of influenza virus neuraminidase, a type II transmembrane glycoprotein, for apical sorting and raft association.
    J Virol. 2000 Jul;74(14):6538-45 PMID: 10864667
  73. Ricin-resistant Madin-Darby canine kidney cells missort a major endogenous apical sialoglycoprotein.
    J Biol Chem. 1993 Apr 5;268(10):6909-16 PMID: 8463221
  74. The role of N-glycosylation in transport to the plasma membrane and sorting of the neuronal glycine transporter GLYT2.
    J Biol Chem. 2001 Jan 19;276(3):2168-73 PMID: 11036075
  75. Structural basis for recognition of high mannose type glycoproteins by mammalian transport lectin VIP36.
    J Biol Chem. 2007 Sep 21;282(38):28246-55 PMID: 17652092
  76. Differential detergent resistance of the apical and basolateral NPPases: relationship with polarized targeting.
    J Cell Sci. 2007 Mar 15;120(Pt 6):1009-16 PMID: 17311850
  77. Apical protein transport.
    Cell Mol Life Sci. 2006 Nov;63(21):2491-505 PMID: 16927027
  78. The binding of VIP36 and alpha-amylase in the secretory vesicles via high-mannose type glycans.
    Glycobiology. 2004 Aug;14(8):739-44 PMID: 15070860
  79. Mutations in the middle of the transmembrane domain reverse the polarity of transport of the influenza virus hemagglutinin in MDCK epithelial cells.
    J Cell Biol. 1998 Jul 13;142(1):51-7 PMID: 9660862
  80. Inverse correlation between the extent of N-glycan branching and intercellular adhesion in epithelia. Contribution of the Na,K-ATPase beta1 subunit.
    J Biol Chem. 2008 Jan 25;283(4):2192-202 PMID: 18025087
  81. N-glycans, not the GPI anchor, mediate the apical targeting of a naturally glycosylated, GPI-anchored protein in polarised epithelial cells.
    J Cell Sci. 2004 Oct 1;117(Pt 21):5079-86 PMID: 15456847
  82. Quaternary structure and apical membrane sorting of the mammalian NaSi-1 sulfate transporter in renal cell lines.
    Int J Biochem Cell Biol. 2007;39(12):2240-51 PMID: 17681482
  83. Requirement for galectin-3 in apical protein sorting.
    Curr Biol. 2006 Feb 21;16(4):408-14 PMID: 16488876
  84. Lipid rafts function in biosynthetic delivery of proteins to the cell surface in yeast.
    Proc Natl Acad Sci U S A. 2000 Mar 28;97(7):3254-9 PMID: 10716729
  85. Apical sorting by galectin-3-dependent glycoprotein clustering.
    Traffic. 2007 Apr;8(4):379-88 PMID: 17319896
  86. Sugar-binding properties of VIP36, an intracellular animal lectin operating as a cargo receptor.
    J Biol Chem. 2005 Nov 4;280(44):37178-82 PMID: 16129679
  87. Role of EDEM in the release of misfolded glycoproteins from the calnexin cycle.
    Science. 2003 Feb 28;299(5611):1397-400 PMID: 12610306
  88. Removal of sialic acid involving Klotho causes cell-surface retention of TRPV5 channel via binding to galectin-1.
    Proc Natl Acad Sci U S A. 2008 Jul 15;105(28):9805-10 PMID: 18606998
  89. The rat liver Na(+)/bile acid cotransporter. Importance of the cytoplasmic tail to function and plasma membrane targeting.
    J Biol Chem. 2001 Mar 2;276(9):6825-33 PMID: 11112779
  90. Intracellular functions of N-linked glycans.
    Science. 2001 Mar 23;291(5512):2364-9 PMID: 11269317
  91. Clusters of VIP-36-positive vesicles between endoplasmic reticulum and Golgi apparatus in GH3 cells.
    Cell Struct Funct. 2003 Jun;28(3):155-63 PMID: 12951436
  92. The lectin ERGIC-53 is a cargo transport receptor for glycoproteins.
    Nat Cell Biol. 1999 Oct;1(6):330-4 PMID: 10559958
  93. VIP36, a novel component of glycolipid rafts and exocytic carrier vesicles in epithelial cells.
    EMBO J. 1994 Apr 1;13(7):1729-40 PMID: 8157011
  94. 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. 2000 Dec;113 Pt 23:4193-202 PMID: 11069764
Article Info
Journal
American journal of physiology. Renal physiology
Abbr.
Am J Physiol Renal Physiol
ISSN
1931-857X
Published
2009-03-00
Epub
2008-00-29
Pages
F459-69
Language
English
Region
United States
NLM ID
100901990
PMCID
PMC2660186
Subset
IM
Grants
NIDDK NIH HHS · R01 DK077149-02 · United States
NIDDK NIH HHS · R01 DK077149 · United States
NIDDK NIH HHS · R01 DK077149-03 · United States
NIDDK NIH HHS · DK-053642 · United States
NIDDK NIH HHS · DK-58333 · United States
NIDDK NIH HHS · DK-077149 · United States
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com