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PMID: 10385524 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Molecular characterization of caveolin association with the Golgi complex: identification of a cis-Golgi targeting domain in the caveolin molecule.

The Journal of cell biology ·Vol. 145 ·No. 7 ·1999-06-28 ·Pages 1443-59

Luetterforst R, Stang E, Zorzi N, Carozzi A, Way M, Parton RG

Abstract

Caveolins are integral membrane proteins which are a major component of caveolae. In addition, caveolins have been proposed to cycle between intracellular compartments and the cell surface but the exact trafficking route and targeting information in the caveolin molecule have not been defined. We show that antibodies against the caveolin scaffolding domain or against the COOH terminus of caveolin-1 show a striking specificity for the Golgi pool of caveolin and do not recognize surface caveolin by immunofluorescence. To analyze the Golgi targeting of caveolin in more detail, caveolin mutants were expressed in fibroblasts. Specific mutants lacking the NH2 terminus were targeted to the cis Golgi but were not detectable in surface caveolae. Moreover, a 32-amino acid segment of the putative COOH-terminal cytoplasmic domain of caveolin-3 was targeted specifically and exclusively to the Golgi complex and could target a soluble heterologous protein, green fluorescent protein, to this compartment. Palmitoylation-deficient COOH-terminal mutants showed negligible association with the Golgi complex. This study defines unique Golgi targeting information in the caveolin molecule and identifies the cis Golgi complex as an intermediate compartment on the caveolin cycling pathway.

MeSH Terms
Amino Acid Sequence Animals Antibodies Caveolin 1 Caveolin 3 Caveolins Cell Line Cell Membrane/chemistry,drug effects,metabolism,ultrastructure Cells, Cultured Conserved Sequence/genetics Fibroblasts Fluorescent Antibody Technique Golgi Apparatus/chemistry,drug effects,metabolism,ultrastructure Humans Intracellular Membranes/chemistry,drug effects,metabolism,ultrastructure Membrane Proteins/analysis,chemistry,genetics,metabolism Microscopy, Immunoelectron Molecular Sequence Data Nocodazole/pharmacology Palmitic Acid/metabolism Protein Binding Protein Sorting Signals Recombinant Fusion Proteins/analysis,biosynthesis,immunology Sequence Deletion Transfection
Chemicals
Antibodies CAV1 protein, human Caveolin 1 Caveolin 3 Caveolins Membrane Proteins Protein Sorting Signals Recombinant Fusion Proteins Palmitic Acid Nocodazole
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Luetterforst R
Centre for Microscopy and Microanalysis, Department of Physiology and Pharmacology, and Centre for Molecular and Cellular Biology, University of Queensland, Brisbane, Queensland 4072, Australia.
Stang E
Zorzi N
Carozzi A
Way M
Parton R G
References (79)
79 references, click to expand
  1. Phosphorylation of caveolin by src tyrosine kinases. The alpha-isoform of caveolin is selectively phosphorylated by v-Src in vivo.
    J Biol Chem. 1996 Feb 16;271(7):3863-8 PMID: 8632005
  2. Oligomerization of VIP21-caveolin in vitro is stabilized by long chain fatty acylation or cholesterol.
    FEBS Lett. 1996 Jun 17;388(2-3):143-9 PMID: 8690074
  3. Caveolae and caveolins.
    Curr Opin Cell Biol. 1996 Aug;8(4):542-8 PMID: 8791446
  4. Src tyrosine kinases, Galpha subunits, and H-Ras share a common membrane-anchored scaffolding protein, caveolin. Caveolin binding negatively regulates the auto-activation of Src tyrosine kinases.
    J Biol Chem. 1996 Nov 15;271(46):29182-90 PMID: 8910575
  5. A role for caveolin in transport of cholesterol from endoplasmic reticulum to plasma membrane.
    J Biol Chem. 1996 Nov 15;271(46):29427-35 PMID: 8910609
  6. Rab11 regulates recycling through the pericentriolar recycling endosome.
    J Cell Biol. 1996 Nov;135(4):913-24 PMID: 8922376
  7. Bound simian virus 40 translocates to caveolin-enriched membrane domains, and its entry is inhibited by drugs that selectively disrupt caveolae.
    Mol Biol Cell. 1996 Nov;7(11):1825-34 PMID: 8930903
  8. Identification, sequence, and expression of an invertebrate caveolin gene family from the nematode Caenorhabditis elegans. Implications for the molecular evolution of mammalian caveolin genes.
    J Biol Chem. 1997 Jan 24;272(4):2437-45 PMID: 8999956
  9. Caveolin-3 associates with developing T-tubules during muscle differentiation.
    J Cell Biol. 1997 Jan 13;136(1):137-54 PMID: 9008709
  10. Major histocompatibility complex class I molecules mediate association of SV40 with caveolae.
    Mol Biol Cell. 1997 Jan;8(1):47-57 PMID: 9017594
  11. Mutational analysis of the properties of caveolin-1. A novel role for the C-terminal domain in mediating homo-typic caveolin-caveolin interactions.
    J Biol Chem. 1997 Feb 14;272(7):4398-403 PMID: 9020162
  12. Caveolin mRNA levels are up-regulated by free cholesterol and down-regulated by oxysterols in fibroblast monolayers.
    Proc Natl Acad Sci U S A. 1997 Apr 15;94(8):3753-8 PMID: 9108050
  13. Functional rafts in cell membranes.
    Nature. 1997 Jun 5;387(6633):569-72 PMID: 9177342
  14. The first 35 amino acids and fatty acylation sites determine the molecular targeting of endothelial nitric oxide synthase into the Golgi region of cells: a green fluorescent protein study.
    J Cell Biol. 1997 Jun 30;137(7):1525-35 PMID: 9199168
  15. Insulin-stimulated tyrosine phosphorylation of caveolin is specific for the differentiated adipocyte phenotype in 3T3-L1 cells.
    J Biol Chem. 1997 Aug 15;272(33):20706-14 PMID: 9252391
  16. Plasmalemmal caveolae and GPI-anchored membrane proteins.
    Curr Opin Cell Biol. 1993 Aug;5(4):647-52 PMID: 7504930
  17. Dominant-negative caveolin inhibits H-Ras function by disrupting cholesterol-rich plasma membrane domains.
    Nat Cell Biol. 1999 Jun;1(2):98-105 PMID: 10559881
  18. Phase separation of integral membrane proteins in Triton X-114 solution.
    J Biol Chem. 1981 Feb 25;256(4):1604-7 PMID: 6257680
  19. Non-coated membrane invaginations are involved in binding and internalization of cholera and tetanus toxins.
    Nature. 1982 Apr 15;296(5858):651-3 PMID: 7070509
  20. Ligands internalized through coated or noncoated invaginations follow a common intracellular pathway.
    Proc Natl Acad Sci U S A. 1987 Nov;84(22):7957-61 PMID: 2446314
  21. Characterization of the early endosome and putative endocytic carrier vesicles in vivo and with an assay of vesicle fusion in vitro.
    J Cell Biol. 1989 Apr;108(4):1301-16 PMID: 2538480
  22. Caveolae: static inpocketings of the plasma membrane, dynamic vesicles or plain artifact?
    J Cell Sci. 1988 Jul;90 ( Pt 3):341-8 PMID: 3075612
  23. Tyrosine phosphorylation of a 22-kDa protein is correlated with transformation by Rous sarcoma virus.
    J Biol Chem. 1989 Dec 5;264(34):20163-6 PMID: 2479645
  24. Role of microtubules in the organisation of the Golgi apparatus.
    Cell Motil Cytoskeleton. 1990;15(2):67-70 PMID: 2178782
  25. Localization of low molecular weight GTP binding proteins to exocytic and endocytic compartments.
    Cell. 1990 Jul 27;62(2):317-29 PMID: 2115402
  26. A new generation of animal cell expression vectors based on the Semliki Forest virus replicon.
    Biotechnology (N Y). 1991 Dec;9(12):1356-61 PMID: 1370252
  27. Endothelial transport of macromolecules: transcytosis and endocytosis. A look from cell biology.
    Cell Biol Rev. 1991;25(1):1-78 PMID: 1764617
  28. Caveolin, a protein component of caveolae membrane coats.
    Cell. 1992 Feb 21;68(4):673-82 PMID: 1739974
  29. VIP21, a 21-kD membrane protein is an integral component of trans-Golgi-network-derived transport vesicles.
    J Cell Biol. 1992 Sep;118(5):1003-14 PMID: 1512286
  30. Sequence and expression of caveolin, a protein component of caveolae plasma membrane domains phosphorylated on tyrosine in Rous sarcoma virus-transformed fibroblasts.
    Proc Natl Acad Sci U S A. 1992 Nov 1;89(21):10517-21 PMID: 1279683
  31. Caveolae and sorting in the trans-Golgi network of epithelial cells.
    EMBO J. 1993 Apr;12(4):1597-605 PMID: 8385608
  32. Expression of heterologous proteins in cultured rat hippocampal neurons using the Semliki Forest virus vector.
    J Neurosci Res. 1993 Jul 1;35(4):445-51 PMID: 8360951
  33. Giantin, a novel conserved Golgi membrane protein containing a cytoplasmic domain of at least 350 kDa.
    Mol Biol Cell. 1993 Jul;4(7):679-93 PMID: 7691276
  34. Retrieval of TGN proteins from the cell surface requires endosomal acidification.
    EMBO J. 1994 May 15;13(10):2305-12 PMID: 8194522
  35. A signal located within amino acids 1-27 of GAD65 is required for its targeting to the Golgi complex region.
    J Cell Biol. 1994 Jul;126(2):331-41 PMID: 8034738
  36. Caveolin moves from caveolae to the Golgi apparatus in response to cholesterol oxidation.
    J Cell Biol. 1994 Dec;127(5):1185-97 PMID: 7962084
  37. Regulated internalization of caveolae.
    J Cell Biol. 1994 Dec;127(5):1199-215 PMID: 7962085
  38. Filipin-sensitive caveolae-mediated transport in endothelium: reduced transcytosis, scavenger endocytosis, and capillary permeability of select macromolecules.
    J Cell Biol. 1994 Dec;127(5):1217-32 PMID: 7525606
  39. Detergent-insoluble glycolipid microdomains in lymphocytes in the absence of caveolae.
    J Biol Chem. 1994 Dec 9;269(49):30745-8 PMID: 7982998
  40. Localization of the Lys, Asp, Glu, Leu tetrapeptide receptor to the Golgi complex and the intermediate compartment in mammalian cells.
    J Cell Biol. 1994 Dec;127(6 Pt 1):1557-74 PMID: 7798312
  41. Targeting of the 67-kDa isoform of glutamic acid decarboxylase to intracellular organelles is mediated by its interaction with the NH2-terminal region of the 65-kDa isoform of glutamic acid decarboxylase.
    J Biol Chem. 1995 Feb 3;270(5):2241-6 PMID: 7836456
  42. Reduction of caveolin and caveolae in oncogenically transformed cells.
    Proc Natl Acad Sci U S A. 1995 Feb 28;92(5):1381-5 PMID: 7877987
  43. Caveolin is palmitoylated on multiple cysteine residues. Palmitoylation is not necessary for localization of caveolin to caveolae.
    J Biol Chem. 1995 Mar 24;270(12):6838-42 PMID: 7896831
  44. Glycolipid-anchored proteins in neuroblastoma cells form detergent-resistant complexes without caveolin.
    J Cell Biol. 1995 May;129(3):619-27 PMID: 7537273
  45. Caveolae, transmembrane signalling and cellular transformation.
    Mol Membr Biol. 1995 Jan-Mar;12(1):121-4 PMID: 7767370
  46. Insulin stimulates the tyrosine phosphorylation of caveolin.
    J Cell Biol. 1995 Jun;129(6):1523-31 PMID: 7540611
  47. Evidence for a regulated interaction between heterotrimeric G proteins and caveolin.
    J Biol Chem. 1995 Jun 30;270(26):15693-701 PMID: 7797570
  48. Mapping the distribution of Golgi enzymes involved in the construction of complex oligosaccharides.
    J Cell Sci. 1995 Apr;108 ( Pt 4):1617-27 PMID: 7615680
  49. The Golgi association of endothelial nitric oxide synthase is necessary for the efficient synthesis of nitric oxide.
    J Biol Chem. 1995 Jul 28;270(30):17641-4 PMID: 7543089
  50. Digging into caveolae.
    Science. 1995 Sep 8;269(5229):1398-9 PMID: 7660120
  51. De novo formation of caveolae in lymphocytes by expression of VIP21-caveolin.
    Proc Natl Acad Sci U S A. 1995 Sep 12;92(19):8655-9 PMID: 7567992
  52. Oligomeric structure of caveolin: implications for caveolae membrane organization.
    Proc Natl Acad Sci U S A. 1995 Sep 26;92(20):9407-11 PMID: 7568142
  53. Chimeric green fluorescent protein as a tool for visualizing subcellular organelles in living cells.
    Curr Biol. 1995 Jun 1;5(6):635-42 PMID: 7552174
  54. VIP21/caveolin is a cholesterol-binding protein.
    Proc Natl Acad Sci U S A. 1995 Oct 24;92(22):10339-43 PMID: 7479780
  55. Intracellular cholesterol transport.
    J Lipid Res. 1997 Aug;38(8):1503-21 PMID: 9300773
  56. Caveolin versus calmodulin. Counterbalancing allosteric modulators of endothelial nitric oxide synthase.
    J Biol Chem. 1997 Oct 10;272(41):25907-12 PMID: 9325323
  57. Interaction of neuronal nitric-oxide synthase with caveolin-3 in skeletal muscle. Identification of a novel caveolin scaffolding/inhibitory domain.
    J Biol Chem. 1997 Nov 7;272(45):28187-90 PMID: 9353265
  58. Two sterol regulatory element-like sequences mediate up-regulation of caveolin gene transcription in response to low density lipoprotein free cholesterol.
    Proc Natl Acad Sci U S A. 1997 Sep 30;94(20):10693-8 PMID: 9380697
  59. Involvement of the transmembrane protein p23 in biosynthetic protein transport.
    J Cell Biol. 1997 Dec 1;139(5):1119-35 PMID: 9382861
  60. Dynamic regulation of endothelial nitric oxide synthase: complementary roles of dual acylation and caveolin interactions.
    Biochemistry. 1998 Jan 6;37(1):193-200 PMID: 9425039
  61. Caveolin transfection results in caveolae formation but not apical sorting of glycosylphosphatidylinositol (GPI)-anchored proteins in epithelial cells.
    J Cell Biol. 1998 Feb 9;140(3):617-26 PMID: 9456321
  62. Caveolin-1 and -2 in the exocytic pathway of MDCK cells.
    J Cell Biol. 1998 Feb 23;140(4):795-806 PMID: 9472032
  63. Caveolins, a family of scaffolding proteins for organizing "preassembled signaling complexes" at the plasma membrane.
    J Biol Chem. 1998 Mar 6;273(10):5419-22 PMID: 9488658
  64. Characterization of a cytosolic heat-shock protein-caveolin chaperone complex. Involvement in cholesterol trafficking.
    J Biol Chem. 1998 Mar 13;273(11):6525-32 PMID: 9497388
  65. Regulation of caveolin and caveolae by cholesterol in MDCK cells.
    J Lipid Res. 1998 Feb;39(2):369-79 PMID: 9507997
  66. A lipid associated with the antiphospholipid syndrome regulates endosome structure and function.
    Nature. 1998 Mar 12;392(6672):193-7 PMID: 9515966
  67. Cholesterol is required for surface transport of influenza virus hemagglutinin.
    J Cell Biol. 1998 Mar 23;140(6):1357-67 PMID: 9508769
  68. The pleckstrin homology domain of oxysterol-binding protein recognises a determinant specific to Golgi membranes.
    Curr Biol. 1998 Jun 18;8(13):729-39 PMID: 9651677
  69. The caveolae membrane system.
    Annu Rev Biochem. 1998;67:199-225 PMID: 9759488
  70. Exploitation of major histocompatibility complex class I molecules and caveolae by simian virus 40.
    Immunol Rev. 1999 Apr;168:23-31 PMID: 10399062
  71. The fine structure of the gall bladder epithelium of the mouse.
    J Biophys Biochem Cytol. 1955 Sep 25;1(5):445-58 PMID: 13263332
  72. Plasma membrane caveolae mediate the efflux of cellular free cholesterol.
    Biochemistry. 1995 Nov 7;34(44):14288-92 PMID: 7578031
  73. VIP21-caveolin, a membrane protein constituent of the caveolar coat, oligomerizes in vivo and in vitro.
    Mol Biol Cell. 1995 Jul;6(7):911-27 PMID: 7579702
  74. A photo-reactive derivative of ganglioside GM1 specifically cross-links VIP21-caveolin on the cell surface.
    FEBS Lett. 1995 Nov 13;375(1-2):11-4 PMID: 7498456
  75. M-caveolin, a muscle-specific caveolin-related protein.
    FEBS Lett. 1995 Nov 27;376(1-2):108-12 PMID: 8521953
  76. Caveolin cycles between plasma membrane caveolae and the Golgi complex by microtubule-dependent and microtubule-independent steps.
    J Cell Biol. 1995 Dec;131(6 Pt 1):1421-33 PMID: 8522601
  77. Identification, sequence, and expression of caveolin-2 defines a caveolin gene family.
    Proc Natl Acad Sci U S A. 1996 Jan 9;93(1):131-5 PMID: 8552590
  78. Molecular cloning of caveolin-3, a novel member of the caveolin gene family expressed predominantly in muscle.
    J Biol Chem. 1996 Jan 26;271(4):2255-61 PMID: 8567687
  79. Co-purification and direct interaction of Ras with caveolin, an integral membrane protein of caveolae microdomains. Detergent-free purification of caveolae microdomains.
    J Biol Chem. 1996 Apr 19;271(16):9690-7 PMID: 8621645
Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
Published
1999-06-28
Pages
1443-59
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2133166
Subset
IM
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