QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Vol. 15, Issue 12, 5399-5407, December 2004

This Article Full Text Full Text (PDF) All Versions of this Article: E04-03-0182v1 15/12/5399    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bared, S. M. Articles by Schmitz, G. Search for Related Content PubMed PubMed Citation Articles by Bared, S. M. Articles by Schmitz, G.

Association of ABCA1 with Syntaxin 13 and Flotillin-1 and Enhanced Phagocytosis in Tangier Cells

Institute of Clinical Chemistry and Laboratory Medicine, University of Regensburg, 93040 Regensburg, Germany

Submitted March 5, 2004; Accepted September 27, 2004
Monitoring Editor: Guido Guidotti

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.

^* Corresponding author. E-mail address: gerd.schmitz{at}klinik.uniregensburg.de.

This article has been cited by other articles:

				G. Schmitz and M. Grandl The Molecular Mechanisms of HDL and Associated Vesicular Trafficking Mechanisms to Mediate Cellular Lipid Homeostasis Arterioscler Thromb Vasc Biol, November 1, 2009; 29(11): 1718 - 1722. [Abstract] [Full Text] [PDF]

				M. D. Linder, M. I. Mayranpaa, J. Peranen, T. E. Pietila, V. M. Pietiainen, R.-L. Uronen, V. M. Olkkonen, P. T. Kovanen, and E. Ikonen Rab8 Regulates ABCA1 Cell Surface Expression and Facilitates Cholesterol Efflux in Primary Human Macrophages Arterioscler Thromb Vasc Biol, June 1, 2009; 29(6): 883 - 888. [Abstract] [Full Text] [PDF]

				C. Munderloh, G. P. Solis, V. Bodrikov, F. A. Jaeger, M. Wiechers, E. Malaga-Trillo, and C. A. O. Stuermer Reggies/Flotillins Regulate Retinal Axon Regeneration in the Zebrafish Optic Nerve and Differentiation of Hippocampal and N2a Neurons J. Neurosci., May 20, 2009; 29(20): 6607 - 6615. [Abstract] [Full Text] [PDF]

				K. Riento, M. Frick, I. Schafer, and B. J. Nichols Endocytosis of flotillin-1 and flotillin-2 is regulated by Fyn kinase J. Cell Sci., April 1, 2009; 122(7): 912 - 918. [Abstract] [Full Text] [PDF]

				A.-A. Raymond, A. G. de Peredo, A. Stella, A. Ishida-Yamamoto, D. Bouyssie, G. Serre, B. Monsarrat, and M. Simon Lamellar Bodies of Human Epidermis: Proteomics Characterization by High Throughput Mass Spectrometry and Possible Involvement of CLIP-170 in their Trafficking/Secretion Mol. Cell. Proteomics, November 1, 2008; 7(11): 2151 - 2175. [Abstract] [Full Text] [PDF]

				M. E. Jacobs, L. V. DeSouza, H. Samaranayake, R. E. Pearlman, K. W. M. Siu, and L. A. Klobutcher The Tetrahymena thermophila Phagosome Proteome Eukaryot. Cell, December 1, 2006; 5(12): 1990 - 2000. [Abstract] [Full Text] [PDF]

				J. A. Corcoran, J. Salsman, R. de Antueno, A. Touhami, M. H. Jericho, E. K. Clancy, and R. Duncan The p14 Fusion-associated Small Transmembrane (FAST) Protein Effects Membrane Fusion from a Subset of Membrane Microdomains J. Biol. Chem., October 20, 2006; 281(42): 31778 - 31789. [Abstract] [Full Text] [PDF]

				N. Iwamoto, S. Abe-Dohmae, R. Sato, and S. Yokoyama ABCA7 expression is regulated by cellular cholesterol through the SREBP2 pathway and associated with phagocytosis J. Lipid Res., September 1, 2006; 47(9): 1915 - 1927. [Abstract] [Full Text] [PDF]

				A. W. Jehle, S. J. Gardai, S. Li, P. Linsel-Nitschke, K. Morimoto, W. J. Janssen, R. W. Vandivier, N. Wang, S. Greenberg, B. M. Dale, et al. ATP-binding cassette transporter A7 enhances phagocytosis of apoptotic cells and associated ERK signaling in macrophages J. Cell Biol., August 14, 2006; 174(4): 547 - 556. [Abstract] [Full Text] [PDF]

				J. F. Oram and J. W. Heinecke ATP-Binding Cassette Transporter A1: A Cell Cholesterol Exporter That Protects Against Cardiovascular Disease Physiol Rev, October 1, 2005; 85(4): 1343 - 1372. [Abstract] [Full Text] [PDF]