Home LiteratureArticle Details
PMID: 15469992 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Association of ABCA1 with syntaxin 13 and flotillin-1 and enhanced phagocytosis in tangier cells.

Molecular biology of the cell ·Vol. 15 ·No. 12 ·2004-12-00 ·Pages 5399-407

Bared SM, Buechler C, Boettcher A, Dayoub R, Sigruener A, Grandl M, Rudolph C, Dada A, Schmitz G

Abstract

The ATP-binding cassette transporter A1 (ABCA1) facilitates the cellular release of cholesterol and choline-phospholipids to apolipoprotein A-I (apoA-I) and several studies indicate that vesicular transport is associated with ABCA1 function. Syntaxins play a major role in vesicular fusion and have also been demonstrated to interact with members of the ABC-transporter family. Therefore, we focused on the identification of syntaxins that directly interact with ABCA1. The expression of syntaxins and ABCA1 in cultured human monocytes during M-CSF differentiation and cholesterol loading was investigated and syntaxins 3, 6, and 13 were found induced in foam cells together with ABCA1. Immunoprecipitation experiments revealed a direct association of syntaxin 13 and full-length ABCA1, whereas syntaxin 3 and 6 failed to interact with ABCA1. The colocalization of ABCA1 and syntaxin 13 was also shown by immunofluorescence microscopy. Silencing of syntaxin 13 by small interfering RNA (siRNA) led to reduced ABCA1 protein levels and hence to a significant decrease in apoA-I-dependent choline-phospholipid efflux. ABCA1 is localized in Lubrol WX-insoluble raft microdomains in macrophages and syntaxin 13 and flotillin-1 were also detected in these detergent resistant microdomains along with ABCA1. Syntaxin 13, flotillin-1, and ABCA1 were identified as phagosomal proteins, indicating the involvement of the phagosomal compartment in ABCA1-mediated lipid efflux. In addition, the uptake of latex phagobeads by fibroblasts with mutated ABCA1 was enhanced when compared with control cells and the recombinant expression of functional ABCA1 normalized the phagocytosis rate in Tangier fibroblasts. It is concluded that ABCA1 forms a complex with syntaxin 13 and flotillin-1, residing at the plasma membrane and in phagosomes that are partially located in raft microdomains.

MeSH Terms
ATP Binding Cassette Transporter 1 ATP-Binding Cassette Transporters/metabolism Adult Cells, Cultured Humans Macrophages/metabolism Membrane Proteins/genetics,metabolism Middle Aged Monocytes/metabolism Phagocytosis Protein Binding Qa-SNARE Proteins RNA, Small Interfering Tangier Disease/metabolism,pathology
Chemicals
ABCA1 protein, human ATP Binding Cassette Transporter 1 ATP-Binding Cassette Transporters Membrane Proteins Qa-SNARE Proteins RNA, Small Interfering flotillins
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Bared Salim Maa
Institute of Clinical Chemistry and Laboratory Medicine, University of Regensburg, 93040 Regensburg, Germany.
Buechler Christa
Boettcher Alfred
Dayoub Rania
Sigruener Alexander
Grandl Margot
Rudolph Christian
Dada Ashraf
Schmitz Gerd
References (50)
50 references, click to expand
  1. Flotillin-1-enriched lipid raft domains accumulate on maturing phagosomes.
    J Biol Chem. 2001 May 25;276(21):18507-12 PMID: 11279173
  2. A rapid method of total lipid extraction and purification.
    Can J Biochem Physiol. 1959 Aug;37(8):911-7 PMID: 13671378
  3. ATP binding cassette transporter ABCA1 modulates the secretion of apolipoprotein E from human monocyte-derived macrophages.
    FASEB J. 2001 Jul;15(9):1555-61 PMID: 11427487
  4. Cellular localization and trafficking of the human ABCA1 transporter.
    J Biol Chem. 2001 Jul 20;276(29):27584-90 PMID: 11349133
  5. CFTR: interacting with everything?
    News Physiol Sci. 2001 Aug;16:167-70 PMID: 11479366
  6. ATP-binding cassette transporter-1 induces rearrangement of actin cytoskeletons possibly through Cdc42/N-WASP.
    Biochem Biophys Res Commun. 2001 Sep 28;287(3):757-65 PMID: 11563861
  7. Endocytosis is enhanced in Tangier fibroblasts: possible role of ATP-binding cassette protein A1 in endosomal vesicular transport.
    J Biol Chem. 2001 Oct 19;276(42):39476-83 PMID: 11504722
  8. ATP-binding cassette transporter A1 mediates cellular secretion of alpha-tocopherol.
    J Biol Chem. 2001 Oct 26;276(43):39898-902 PMID: 11546785
  9. Characterization of the ATPase cycle of human ABCA1: implications for its function as a regulator rather than an active transporter.
    Biochem Biophys Res Commun. 2001 Nov 16;288(5):1258-64 PMID: 11700048
  10. Preferential ATP-binding cassette transporter A1-mediated cholesterol efflux from late endosomes/lysosomes.
    J Biol Chem. 2001 Nov 23;276(47):43564-9 PMID: 11559713
  11. Apolipoprotein AI and HDL(3) inhibit spreading of primary human monocytes through a mechanism that involves cholesterol depletion and regulation of CDC42.
    Atherosclerosis. 2001 Dec;159(2):313-24 PMID: 11730811
  12. The syntaxins.
    Genome Biol. 2001;2(11):REVIEWS3012 PMID: 11737951
  13. Non-conventional trafficking of the cystic fibrosis transmembrane conductance regulator through the early secretory pathway.
    J Biol Chem. 2002 Mar 29;277(13):11401-9 PMID: 11799116
  14. Apo AI/ABCA1-dependent and HDL3-mediated lipid efflux from compositionally distinct cholesterol-based microdomains.
    Traffic. 2002 Apr;3(4):268-78 PMID: 11929608
  15. The carboxyterminus of the ATP-binding cassette transporter A1 interacts with a beta2-syntrophin/utrophin complex.
    Biochem Biophys Res Commun. 2002 May 3;293(2):759-65 PMID: 12054535
  16. Up-regulation of human deoxyribonuclease II gene expression during myelomonocytic differentiation of HL-60 and THP-1 cells.
    Biochem Biophys Res Commun. 2002 Aug 9;296(1):48-53 PMID: 12147225
  17. Naturally occurring mutations in the largest extracellular loops of ABCA1 can disrupt its direct interaction with apolipoprotein A-I.
    J Biol Chem. 2002 Sep 6;277(36):33178-87 PMID: 12084722
  18. Syntaxins 13 and 7 function at distinct steps during phagocytosis.
    J Immunol. 2002 Sep 15;169(6):3250-6 PMID: 12218144
  19. CFTR chloride channels are regulated by a SNAP-23/syntaxin 1A complex.
    Proc Natl Acad Sci U S A. 2002 Sep 17;99(19):12477-82 PMID: 12209004
  20. The molecular machinery for the biogenesis of lysosome-related organelles: lessons from Hermansky-Pudlak syndrome.
    Semin Cell Dev Biol. 2002 Aug;13(4):271-8 PMID: 12243726
  21. Molecular and functional interaction of the ATP-binding cassette transporter A1 with Fas-associated death domain protein.
    J Biol Chem. 2002 Nov 1;277(44):41307-10 PMID: 12235128
  22. Retarded intracellular lipid transport associated with reduced expression of Cdc42, a member of Rho-GTPases, in human aged skin fibroblasts: a possible function of Cdc42 in mediating intracellular lipid transport.
    Arterioscler Thromb Vasc Biol. 2002 Nov 1;22(11):1899-904 PMID: 12426222
  23. ABCA1: regulation, trafficking and association with heteromeric proteins.
    Ann Med. 2002;34(5):334-47 PMID: 12452478
  24. Ectopic beta-chain of ATP synthase is an apolipoprotein A-I receptor in hepatic HDL endocytosis.
    Nature. 2003 Jan 2;421(6918):75-9 PMID: 12511957
  25. ABCA1 and the engulfment of apoptotic cells.
    Biochim Biophys Acta. 2002 Dec 30;1585(2-3):64-71 PMID: 12531538
  26. Glycosphingolipids internalized via caveolar-related endocytosis rapidly merge with the clathrin pathway in early endosomes and form microdomains for recycling.
    J Biol Chem. 2003 Feb 28;278(9):7564-72 PMID: 12482757
  27. Secretory vesicular transport from the Golgi is altered during ATP-binding cassette protein A1 (ABCA1)-mediated cholesterol efflux.
    J Biol Chem. 2003 Mar 21;278(12):10002-5 PMID: 12551894
  28. Felic (CIP4b), a novel binding partner with the Src kinase Lyn and Cdc42, localizes to the phagocytic cup.
    Blood. 2003 Apr 1;101(7):2804-9 PMID: 12456510
  29. Lipid rafts: bringing order to chaos.
    J Lipid Res. 2003 Apr;44(4):655-67 PMID: 12562849
  30. Alpha1-syntrophin modulates turnover of ABCA1.
    J Biol Chem. 2004 Apr 9;279(15):15091-5 PMID: 14722086
  31. Linking albinism and immunity: the secrets of secretory lysosomes.
    Science. 2004 Jul 2;305(5680):55-9 PMID: 15232098
  32. Transport of lipids from golgi to plasma membrane is defective in tangier disease patients and Abc1-deficient mice.
    Nat Genet. 2000 Feb;24(2):192-6 PMID: 10655069
  33. The phagosome proteome: insight into phagosome functions.
    J Cell Biol. 2001 Jan 8;152(1):165-80 PMID: 11149929
  34. Accumulation of RhoA, RhoB, RhoG, and Rac1 in fibroblasts from Tangier disease subjects suggests a regulatory role of Rho family proteins in cholesterol efflux.
    Biochem Biophys Res Commun. 2001 Jan 12;280(1):229-36 PMID: 11162504
  35. Flotillin-1: gene structure: cDNA cloning from human lung and the identification of alternative polyadenylation signals.
    Int J Biochem Cell Biol. 2001 Jan;33(1):53-64 PMID: 11167132
  36. Differences in the mode of phagocytosis with Fc and C3 receptors in macrophages.
    Scand J Immunol. 1977;6(8):797-807 PMID: 561436
  37. Interaction of high density lipoproteins with cholesteryl ester-laden macrophages: biochemical and morphological characterization of cell surface receptor binding, endocytosis and resecretion of high density lipoproteins by macrophages.
    EMBO J. 1985 Mar;4(3):613-22 PMID: 2988931
  38. In vivo metabolism of proapolipoprotein A-I in Tangier disease.
    J Clin Invest. 1987 Dec;80(6):1742-7 PMID: 3119665
  39. Biogenesis of phagolysosomes proceeds through a sequential series of interactions with the endocytic apparatus.
    J Cell Biol. 1994 Mar;124(5):677-88 PMID: 8120091
  40. Characterization and subcellular localization of target membrane soluble NSF attachment protein receptors (t-SNAREs) in macrophages. Syntaxins 2, 3, and 4 are present on phagosomal membranes.
    J Immunol. 1996 Jun 1;156(11):4377-83 PMID: 8666810
  41. Peripheral blood mononuclear phagocyte subpopulations as cellular markers in hypercholesterolemia.
    Arterioscler Thromb Vasc Biol. 1996 Dec;16(12):1437-47 PMID: 8977447
  42. Interleukin-1beta secretion is impaired by inhibitors of the Atp binding cassette transporter, ABC1.
    Blood. 1997 Oct 15;90(8):2911-5 PMID: 9376570
  43. Syntaxin 13 mediates cycling of plasma membrane proteins via tubulovesicular recycling endosomes.
    J Cell Biol. 1998 Nov 16;143(4):957-71 PMID: 9817754
  44. Identification of two distinct mechanisms of phagocytosis controlled by different Rho GTPases.
    Science. 1998 Nov 27;282(5394):1717-21 PMID: 9831565
  45. Molecular cloning of the human ATP-binding cassette transporter 1 (hABC1): evidence for sterol-dependent regulation in macrophages.
    Biochem Biophys Res Commun. 1999 Apr 2;257(1):29-33 PMID: 10092505
  46. Mutations in ABC1 in Tangier disease and familial high-density lipoprotein deficiency.
    Nat Genet. 1999 Aug;22(4):336-45 PMID: 10431236
  47. The gene encoding ATP-binding cassette transporter 1 is mutated in Tangier disease.
    Nat Genet. 1999 Aug;22(4):347-51 PMID: 10431237
  48. Tangier disease is caused by mutations in the gene encoding ATP-binding cassette transporter 1.
    Nat Genet. 1999 Aug;22(4):352-5 PMID: 10431238
  49. Cholesterol efflux to apolipoprotein AI involves endocytosis and resecretion in a calcium-dependent pathway.
    Proc Natl Acad Sci U S A. 1999 Sep 28;96(20):11358-63 PMID: 10500181
  50. Adipophilin is a sensitive marker for lipid loading in human blood monocytes.
    Biochim Biophys Acta. 2001 May 31;1532(1-2):97-104 PMID: 11420178
Article Info
Journal
Molecular biology of the cell
Abbr.
Mol Biol Cell
ISSN
1059-1524
DOI
10.1091/mbc.e04-03-0182
Published
2004-12-00
Epub
2004-00-06
Pages
5399-407
Language
English
Region
United States
NLM ID
9201390
PMCID
PMC532019
Subset
IM
External Links
PubMed source DOI: 10.1091/mbc.e04-03-0182 PMC Full Text View journal details
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

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2