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PMID: 16087710 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Transcytosis of NgCAM in epithelial cells reflects differential signal recognition on the endocytic and secretory pathways.

The Journal of cell biology ·Vol. 170 ·No. 4 ·2005-08-15 ·Pages 595-605

Anderson E, Maday S, Sfakianos J, Hull M, Winckler B, Sheff D, Fölsch H, Mellman I

Abstract

NgCAM is a cell adhesion molecule that is largely axonal in neurons and apical in epithelia. In Madin-Darby canine kidney cells, NgCAM is targeted to the apical surface by transcytosis, being first inserted into the basolateral domain from which it is internalized and transported to the apical domain. Initial basolateral transport is mediated by a sequence motif (Y(33)RSL) decoded by the AP-1B clathrin adaptor complex. This motif is a substrate in vitro for tyrosine phosphorylation by p60src, a modification that disrupts NgCAM's ability to interact with clathrin adaptors. Based on the behavior of various NgCAM mutants, it appears that after arrival at the basolateral surface, the AP-1B interaction site is silenced by phosphorylation of Tyr(33). This slows endocytosis and inhibits basolateral recycling from endosomes, resulting in NgCAM transcytosis due to a cryptic apical targeting signal in its extracellular domain. Thus, transcytosis of NgCAM and perhaps other membrane proteins may reflect the spatial regulation of recognition by adaptors such as AP-1B.

MeSH Terms
Adaptor Protein Complex 1/metabolism Amino Acid Sequence Animals Cell Adhesion Molecules/metabolism Cell Polarity Cytoplasm/metabolism Dogs Endocytosis Epithelial Cells/cytology,metabolism Molecular Sequence Data Phosphotyrosine/metabolism Protein Binding Protein Structure, Tertiary Protein Transport Signal Transduction
Chemicals
Adaptor Protein Complex 1 Cell Adhesion Molecules Phosphotyrosine
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Anderson Eric
Department of Cell Biology, Ludwig Institute for Cancer Research, Yale University School of Medicine, New Haven, CT 06520, USA.
Maday Sandra
Sfakianos Jeff
Hull Michael
Winckler Bettina
Sheff David
Fölsch Heike
Mellman Ira
References (73)
73 references, click to expand
  1. CAMs and axonal growth: a critical evaluation of the role of calcium and the MAPK cascade.
    Mol Cell Neurosci. 2000 Oct;16(4):283-95 PMID: 11085868
  2. Distribution and function of AP-1 clathrin adaptor complexes in polarized epithelial cells.
    J Cell Biol. 2001 Feb 5;152(3):595-606 PMID: 11157985
  3. Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells.
    Nature. 2001 May 24;411(6836):494-8 PMID: 11373684
  4. A novel cellular phenotype for familial hypercholesterolemia due to a defect in polarized targeting of LDL receptor.
    Cell. 2001 Jun 1;105(5):575-85 PMID: 11389828
  5. Transcytosis of the polymeric Ig receptor requires phosphorylation of serine 664 in the absence but not the presence of dimeric IgA.
    Cell. 1993 Jul 30;74(2):245-55 PMID: 8343953
  6. Common signals control low density lipoprotein receptor sorting in endosomes and the Golgi complex of MDCK cells.
    Cell. 1993 Sep 24;74(6):1053-64 PMID: 8402881
  7. Mutational and secondary structural analysis of the basolateral sorting signal of the polymeric immunoglobulin receptor.
    J Cell Biol. 1993 Dec;123(5):1149-60 PMID: 8245123
  8. Stimulation of transcytosis of the polymeric immunoglobulin receptor by dimeric IgA.
    Proc Natl Acad Sci U S A. 1994 Jan 4;91(1):163-6 PMID: 8278358
  9. Basolateral to apical transcytosis in polarized cells is indirect and involves BFA and trimeric G protein sensitive passage through the apical endosome.
    J Cell Biol. 1994 Jan;124(1-2):83-100 PMID: 7905002
  10. The neural recognition molecule L1 is a sialic acid-binding lectin for CD24, which induces promotion and inhibition of neurite outgrowth.
    J Biol Chem. 2001 Jun 15;276(24):21656-63 PMID: 11283023
  11. FIGQY phosphorylation defines discrete populations of L1 cell adhesion molecules at sites of cell-cell contact and in migrating neurons.
    J Cell Sci. 2001 Nov;114(Pt 21):3823-35 PMID: 11719549
  12. Protein trafficking in the exocytic pathway of polarized epithelial cells.
    Trends Cell Biol. 2001 Dec;11(12):483-6 PMID: 11719053
  13. A system for stable expression of short interfering RNAs in mammalian cells.
    Science. 2002 Apr 19;296(5567):550-3 PMID: 11910072
  14. Functional binding interaction identified between the axonal CAM L1 and members of the ERM family.
    J Cell Biol. 2002 Jun 24;157(7):1105-12 PMID: 12070130
  15. L1 endocytosis is controlled by a phosphorylation-dephosphorylation cycle stimulated by outside-in signaling by L1.
    J Cell Biol. 2002 Jun 24;157(7):1223-32 PMID: 12082080
  16. Altered trafficking and epithelial cell polarity in disease.
    Trends Cell Biol. 2002 Aug;12(8):374-81 PMID: 12191914
  17. A new activity of doublecortin in recognition of the phospho-FIGQY tyrosine in the cytoplasmic domain of neurofascin.
    J Neurosci. 2002 Sep 15;22(18):7948-58 PMID: 12223548
  18. Retroviral delivery of small interfering RNA into primary cells.
    Proc Natl Acad Sci U S A. 2002 Nov 12;99(23):14943-5 PMID: 12417750
  19. Recycling endosomes can serve as intermediates during transport from the Golgi to the plasma membrane of MDCK cells.
    J Cell Biol. 2004 Nov 8;167(3):531-43 PMID: 15534004
  20. L1-mediated branching is regulated by two ezrin-radixin-moesin (ERM)-binding sites, the RSLE region and a novel juxtamembrane ERM-binding region.
    J Neurosci. 2005 Jan 12;25(2):395-403 PMID: 15647482
  21. Two distinct mechanisms target membrane proteins to the axonal surface.
    Neuron. 2003 Feb 20;37(4):611-24 PMID: 12597859
  22. Transcytosis: crossing cellular barriers.
    Physiol Rev. 2003 Jul;83(3):871-932 PMID: 12843411
  23. Uncovering multiple axonal targeting pathways in hippocampal neurons.
    J Cell Biol. 2003 Sep 29;162(7):1317-28 PMID: 14517209
  24. Signals for sorting of transmembrane proteins to endosomes and lysosomes.
    Annu Rev Biochem. 2003;72:395-447 PMID: 12651740
  25. Delivery of raft-associated, GPI-anchored proteins to the apical surface of polarized MDCK cells by a transcytotic pathway.
    Nat Cell Biol. 2004 Apr;6(4):297-307 PMID: 15048124
  26. Generation of single and double knockdowns in polarized epithelial cells by retrovirus-mediated RNA interference.
    Proc Natl Acad Sci U S A. 2004 Apr 6;101(14):4912-7 PMID: 15051873
  27. The mammalian retromer regulates transcytosis of the polymeric immunoglobulin receptor.
    Nat Cell Biol. 2004 Aug;6(8):763-9 PMID: 15247922
  28. Polymeric immunoglobulin receptor expressed in MDCK cells transcytoses IgA.
    Cell. 1986 Aug 15;46(4):613-21 PMID: 3524859
  29. Phosphorylation of the polymeric immunoglobulin receptor required for its efficient transcytosis.
    Science. 1990 May 11;248(4956):742-5 PMID: 2110383
  30. Structure of the chicken neuron-glia cell adhesion molecule, Ng-CAM: origin of the polypeptides and relation to the Ig superfamily.
    J Cell Biol. 1991 Mar;112(5):1017-29 PMID: 1705558
  31. An autonomous signal for basolateral sorting in the cytoplasmic domain of the polymeric immunoglobulin receptor.
    Cell. 1991 Jul 12;66(1):65-75 PMID: 2070419
  32. Basolateral sorting in MDCK cells requires a distinct cytoplasmic domain determinant.
    Cell. 1991 Sep 6;66(5):907-20 PMID: 1909606
  33. Basolateral sorting of LDL receptor in MDCK cells: the cytoplasmic domain contains two tyrosine-dependent targeting determinants.
    Cell. 1992 Nov 27;71(5):741-53 PMID: 1423629
  34. Ankyrin-binding proteins related to nervous system cell adhesion molecules: candidates to provide transmembrane and intercellular connections in adult brain.
    J Cell Biol. 1993 Apr;121(1):121-33 PMID: 8458865
  35. Receptor-mediated transcytosis of IgA in MDCK cells is via apical recycling endosomes.
    J Cell Biol. 1994 Apr;125(1):67-86 PMID: 8138576
  36. Polarized sorting of the polymeric immunoglobulin receptor in the exocytotic and endocytotic pathways is controlled by the same amino acids.
    EMBO J. 1994 May 15;13(10):2297-304 PMID: 8194521
  37. Rapid internalization of the polymeric immunoglobulin receptor requires phosphorylated serine 726.
    J Biol Chem. 1994 Jun 3;269(22):15676-82 PMID: 8195218
  38. Inhibition of heat shock protein HSP90-pp60v-src heteroprotein complex formation by benzoquinone ansamycins: essential role for stress proteins in oncogenic transformation.
    Proc Natl Acad Sci U S A. 1994 Aug 30;91(18):8324-8 PMID: 8078881
  39. Mechanisms of cell polarity: sorting and transport in epithelial cells.
    Curr Opin Cell Biol. 1994 Aug;6(4):545-54 PMID: 7986532
  40. N-glycans as apical sorting signals in epithelial cells.
    Nature. 1995 Nov 2;378(6552):96-8 PMID: 7477300
  41. Origins of cell polarity.
    Cell. 1996 Feb 9;84(3):335-44 PMID: 8608587
  42. Involvement of p90rsk in neurite outgrowth mediated by the cell adhesion molecule L1.
    J Biol Chem. 1996 Jul 26;271(30):18217-23 PMID: 8663493
  43. Continuous renewal of the axonal pathway sensor apparatus by insertion of new sensor molecules into the growth cone membrane.
    Curr Biol. 1996 Sep 1;6(9):1153-8 PMID: 8805367
  44. The basolateral sorting signal of the polymeric immunoglobulin receptor contains two functional domains.
    J Cell Sci. 1996 Aug;109 ( Pt 8):2133-9 PMID: 8856509
  45. Endocytosis and molecular sorting.
    Annu Rev Cell Dev Biol. 1996;12:575-625 PMID: 8970738
  46. Mutational analysis of the L1 neuronal cell adhesion molecule identifies membrane-proximal amino acids of the cytoplasmic domain that are required for cytoskeletal anchorage.
    Mol Cell Neurosci. 1997;9(2):144-56 PMID: 9245498
  47. The phosphorylation state of the FIGQY tyrosine of neurofascin determines ankyrin-binding activity and patterns of cell segregation.
    Proc Natl Acad Sci U S A. 1997 Nov 25;94(24):12957-62 PMID: 9371782
  48. A single immunoglobulin-like domain of the human neural cell adhesion molecule L1 supports adhesion by multiple vascular and platelet integrins.
    J Cell Biol. 1997 Dec 15;139(6):1567-81 PMID: 9396761
  49. Neural cell adhesion molecules of the immunoglobulin superfamily: role in axon growth and guidance.
    Annu Rev Cell Dev Biol. 1997;13:425-56 PMID: 9442880
  50. Carbohydrate-mediated Golgi to cell surface transport and apical targeting of membrane proteins.
    EMBO J. 1998 Apr 1;17(7):1919-29 PMID: 9524115
  51. Dimerization of the polymeric immunoglobulin receptor controls its transcytotic trafficking.
    Mol Biol Cell. 1998 Apr;9(4):901-15 PMID: 9529387
  52. Multi-ligand interactions with receptor-like protein tyrosine phosphatase beta: implications for intercellular signaling.
    Trends Biochem Sci. 1998 Apr;23(4):121-4 PMID: 9584610
  53. The polarized sorting of membrane proteins expressed in cultured hippocampal neurons using viral vectors.
    Neuron. 1998 May;20(5):855-67 PMID: 9620691
  54. The neural cell adhesion molecule L1 interacts with the AP-2 adaptor and is endocytosed via the clathrin-mediated pathway.
    J Neurosci. 1998 Jul 15;18(14):5311-21 PMID: 9651214
  55. Role of tyrosine phosphorylation in ligand-induced regulation of transcytosis of the polymeric Ig receptor.
    Mol Biol Cell. 1998 Jul;9(7):1787-802 PMID: 9658171
  56. Tyrosine-based membrane protein sorting signals are differentially interpreted by polarized Madin-Darby canine kidney and LLC-PK1 epithelial cells.
    J Biol Chem. 1998 Oct 9;273(41):26862-9 PMID: 9756932
  57. Protein and lipid sorting from the trans-Golgi network to the plasma membrane in polarized cells.
    Semin Cell Dev Biol. 1998 Oct;9(5):503-9 PMID: 9835637
  58. A diffusion barrier maintains distribution of membrane proteins in polarized neurons.
    Nature. 1999 Feb 25;397(6721):698-701 PMID: 10067893
  59. Basolateral sorting of furin in MDCK cells requires a phenylalanine-isoleucine motif together with an acidic amino acid cluster.
    Mol Cell Biol. 1999 Apr;19(4):3136-44 PMID: 10082580
  60. Mu1B, a novel adaptor medium chain expressed in polarized epithelial cells.
    FEBS Lett. 1999 Apr 23;449(2-3):215-20 PMID: 10338135
  61. Glycans in post-Golgi apical targeting: sorting signals or structural props?
    Trends Cell Biol. 1999 Aug;9(8):291-4 PMID: 10407407
  62. Local presentation of substrate molecules directs axon specification by cultured hippocampal neurons.
    J Neurosci. 1999 Aug 1;19(15):6417-26 PMID: 10414970
  63. Neuronal polarity: controlling the sorting and diffusion of membrane components.
    Neuron. 1999 Aug;23(4):637-40 PMID: 10482229
  64. The building blocks for basolateral vesicles in polarized epithelial cells.
    Trends Cell Biol. 2005 Apr;15(4):222-8 PMID: 15817379
  65. A novel clathrin adaptor complex mediates basolateral targeting in polarized epithelial cells.
    Cell. 1999 Oct 15;99(2):189-98 PMID: 10535737
  66. The SRC family protein tyrosine kinase p62yes controls polymeric IgA transcytosis in vivo.
    Mol Cell. 1999 Oct;4(4):627-32 PMID: 10549294
  67. Immunolocalization of the neural cell adhesion molecule L1 in epithelia of rodents.
    Cell Tissue Res. 1999 Nov;298(2):261-73 PMID: 10571115
  68. Activation of the MAPK signal cascade by the neural cell adhesion molecule L1 requires L1 internalization.
    J Biol Chem. 1999 Dec 31;274(53):37965-73 PMID: 10608864
  69. Epithelial polarity: sorting out the sorters.
    Curr Biol. 2000 Jan 13;10(1):R39-42 PMID: 10660294
  70. Structural and functional evolution of the L1 family: are four adhesion molecules better than one?
    Mol Cell Neurosci. 2000 Jan;15(1):1-10 PMID: 10662501
  71. Plasmin-sensitive dibasic sequences in the third fibronectin-like domain of L1-cell adhesion molecule (CAM) facilitate homomultimerization and concomitant integrin recruitment.
    J Cell Biol. 2000 Jun 26;149(7):1485-502 PMID: 10871287
  72. Membrane traffic in polarized epithelial cells.
    Curr Opin Cell Biol. 2000 Aug;12(4):483-90 PMID: 10873817
  73. IgCAMs: bidirectional signals underlying neurite growth.
    Curr Opin Cell Biol. 2000 Oct;12(5):598-605 PMID: 10978896
Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.200506051
Published
2005-08-15
Epub
2005-00-08
Pages
595-605
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2171499
Subset
IM
Grants
NIGMS NIH HHS · R01 GM029765 · United States
NIGMS NIH HHS · GM29765 · United States
External Links
PubMed source DOI: 10.1083/jcb.200506051 PMC Full Text View journal details
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