Startseite Lebenswissenschaften Raft association and lipid droplet targeting of flotillins are independent of caveolin
Artikel
Lizenziert
Nicht lizenziert Erfordert eine Authentifizierung

Raft association and lipid droplet targeting of flotillins are independent of caveolin

  • Lawrence Rajendran , Soazig Le Lay und Harald Illges
Veröffentlicht/Copyright: 5. März 2007
Biological Chemistry
Aus der Zeitschrift Band 388 Heft 3

Abstract

Lipid rafts are liquid ordered platforms that dynamically compartmentalize membranes. Caveolins and flotillins constitute a group of proteins that are enriched in these domains. Caveolin-1 has been shown to be an essential component of caveolae. Flotillins were also discovered as an integral component of caveolae and have since been suggested to interact with caveolins. However, flotillins are also expressed in non-caveolae-containing cells such as lymphocytes and neuronal cells. Hence, a discrepancy exists in the literature regarding the caveolin dependence of flotillin expression and their subcellular localization. To address this controversy, we used mouse embryonic fibroblasts (MEFs) from caveolin-1 knockout (Cav-1-/-) and wild-type mice to study flotillin expression and localization. Here we show that both membrane association and lipid raft partitioning of flotillins are not perturbed in Cav-1-/- MEFs, whereas membrane targeting and raft partitioning of caveolin-2, another caveolin family protein, is severely impaired. Moreover, we demonstrate that flotillin-1, but not flotillin-2, associates with lipid droplets upon oleic acid treatment and that this association is completely independent of caveolin. Taken together, our results show that flotillins are localized in lipid rafts independent of caveolin-1 and that translocation of flotillin-1 to lipid droplets is a caveolin-independent process.

:

Corresponding author

References

Abrami, L., Liu, S., Cosson, P., Leppla, S.H., and van der Goot, F.G. (2003). Anthrax toxin triggers endocytosis of its receptor via a lipid raft-mediated clathrin-dependent process. J. Cell Biol.160, 321–328.10.1083/jcb.200211018Suche in Google Scholar

Baumann, C.A., Ribon, V., Kanzaki, M., Thurmond, D.C., Mora, S., Shigematsu, S., Bickel, P.E., Pessin, J.E., and Saltiel, A.R. (2000). CAP defines a second signalling pathway required for insulin-stimulated glucose transport. Nature407, 202–207.10.1038/35025089Suche in Google Scholar

Bickel, P.E., Scherer, P.E., Schnitzer, J.E., Oh, P., Lisanti, M.P., and Lodish, H.F. (1997). Flotillin and epidermal surface antigen define a new family of caveolae-associated integral membrane proteins. J. Biol. Chem.272, 13793–13802.10.1074/jbc.272.21.13793Suche in Google Scholar

Brasaemle, D.L., Dolios, G., Shapiro, L., and Wang, R. (2004). Proteomic analysis of proteins associated with lipid droplets of basal and lipolytically stimulated 3T3-L1 adipocytes. J. Biol. Chem.279, 46835–46842.10.1074/jbc.M409340200Suche in Google Scholar

Breuza, L., Corby, S., Arsanto, J.P., Delgrossi, M.H., Scheiffele, P., and Le Bivic, A. (2002). The scaffolding domain of caveolin 2 is responsible for its Golgi localization in Caco-2 cells. J. Cell Sci.115, 4457–4467.10.1242/jcs.00130Suche in Google Scholar

Campbell, S.M., Crowe, S.M., and Mak, J. (2001). Lipid rafts and HIV-1: from viral entry to assembly of progeny virions. J. Clin. Virol.22, 217–227.10.1016/S1386-6532(01)00193-7Suche in Google Scholar

Deininger, S.O., Rajendran, L., Lottspeich, F., Przybylski, M., Illges, H., Stuermer, C.A., and Reuter, A. (2003). Identification of teleost Thy-1 and association with the microdomain/lipid raft reggie proteins in regenerating CNS axons. Mol. Cell. Neurosci.22, 544–554.10.1016/S1044-7431(03)00028-9Suche in Google Scholar

Dermine, J.F., Duclos, S., Garin, J., St-Louis, F., Rea, S., Parton, R.G., and Desjardins, M. (2001). Flotillin-1-enriched lipid raft domains accumulate on maturing phagosomes. J. Biol. Chem.276, 18507–18512.10.1074/jbc.M101113200Suche in Google Scholar PubMed

Drab, M., Verkade, P., Elger, M., Kasper, M., Lohn, M., Lauterbach, B., Menne, J., Lindschau, C., Mende, F., Luft, F.C.,et al. (2001). Loss of caveolae, vascular dysfunction, and pulmonary defects in caveolin-1 gene-disrupted mice. Science293, 2449–2452.10.1126/science.1062688Suche in Google Scholar PubMed

Edidin, M. (2003). The state of lipid rafts: from model membranes to cells. Annu. Rev. Biophys. Biomol. Struct.32, 257–283.10.1146/annurev.biophys.32.110601.142439Suche in Google Scholar PubMed

Ehehalt, R., Keller, P., Haass, C., Thiele, C., and Simons, K. (2003). Amyloidogenic processing of the Alzheimer β-amyloid precursor protein depends on lipid rafts. J. Cell Biol.160, 113–123.10.1083/jcb.200207113Suche in Google Scholar

Fra, A.M., Williamson, E., Simons, K., and Parton, R.G. (1995). De novo formation of caveolae in lymphocytes by expression of VIP21-caveolin. Proc. Natl. Acad. Sci. USA92, 8655–8659.10.1073/pnas.92.19.8655Suche in Google Scholar

Fujimoto, T., Kogo, H., Ishiguro, K., Tauchi, K., and Nomura, R. (2001). Caveolin-2 is targeted to lipid droplets, a new ‘membrane domain’ in the cell. J. Cell Biol.152, 1079–1085.10.1083/jcb.152.5.1079Suche in Google Scholar

Galbiati, F., Engelman, J.A., Volonte, D., Zhang, X.L., Minetti, C., Li, M., Hou, H. Jr., Kneitz, B., Edelmann, W., and Lisanti, M.P. (2001). Caveolin-3 null mice show a loss of caveolae, changes in the microdomain distribution of the dystrophin-glycoprotein complex, and t-tubule abnormalities. J. Biol. Chem.276, 21425–21433.10.1074/jbc.M100828200Suche in Google Scholar

Glebov, O.O., Bright, N.A., and Nichols, B.J. (2006). Flotillin-1 defines a clathrin-independent endocytic pathway in mammalian cells. Nat. Cell Biol.8, 46–54.10.1038/ncb1342Suche in Google Scholar

Hooper, N.M. (2005). Roles of proteolysis and lipid rafts in the processing of the amyloid precursor protein and prion protein. Biochem. Soc. Trans.33, 335–338.10.1042/BST0330335Suche in Google Scholar

Kurzchalia, T. (2003). Anthrax toxin rafts into cells. J. Cell Biol.160, 295–296.10.1083/jcb.200301032Suche in Google Scholar

Kurzchalia, T.V., and Parton, R.G. (1999). Membrane microdomains and caveolae. Curr. Opin. Cell Biol.11, 424–431.10.1016/S0955-0674(99)80061-1Suche in Google Scholar

Lang, D.M., Lommel, S., Jung, M., Ankerhold, R., Petrausch, B., Laessing, U., Wiechers, M.F., Plattner, H., and Stuermer, C.A. (1998). Identification of reggie-1 and reggie-2 as plasma membrane-associated proteins which cocluster with activated GPI-anchored cell adhesion molecules in non-caveolar micropatches in neurons. J. Neurobiol.37, 502–523.10.1002/(SICI)1097-4695(199812)37:4<502::AID-NEU2>3.0.CO;2-SSuche in Google Scholar

Le Lay, S., Hajduch, E., Lindsay, M.R., Le Liepvre, X., Thiele, C., Ferre, P., Parton, R.G., Kurzchalia, T., Simons, K., and Dugail, I. (2006). Cholesterol-induced caveolin targeting to lipid droplets in adipocytes: a role for caveolar endocytosis. Traffic7, 549–561.10.1111/j.1600-0854.2006.00406.xSuche in Google Scholar

Lencer, W.I. (2001). Microbes and microbial toxins: paradigms for microbial-mucosal toxins. V. Cholera: invasion of the intestinal epithelial barrier by a stably folded protein toxin. Am. J. Physiol. Gastrointest. Liver Physiol.280, G781–786.Suche in Google Scholar

Liu, J., Deyoung, S.M., Zhang, M., Dold, L.H., and Saltiel, A.R. (2005). The stomatin/prohibitin/flotillin/HflK/C domain of flotillin-1 contains distinct sequences that direct plasma membrane localization and protein interactions in 3T3-L1 adipocytes. J. Biol. Chem.280, 16125–16134.10.1074/jbc.M500940200Suche in Google Scholar

Liu, P., Ying, Y., Zhao, Y., Mundy, D.I., Zhu, M., and Anderson, R.G. (2004). Chinese hamster ovary K2 cell lipid droplets appear to be metabolic organelles involved in membrane traffic. J. Biol. Chem.279, 3787–3792.10.1074/jbc.M311945200Suche in Google Scholar

Malaga-Trillo, E., Laessing, U., Lang, D.M., Meyer, A., and Stuermer, C.A. (2002). Evolution of duplicated reggie genes in zebrafish and goldfish. J. Mol. Evol.54, 235–245.10.1007/s00239-001-0005-1Suche in Google Scholar

Martin, S. and Parton, R.G. (2005). Caveolin, cholesterol, and lipid bodies. Semin. Cell Dev. Biol.16, 163–174.10.1016/j.semcdb.2005.01.007Suche in Google Scholar

Neumann-Giesen, C., Falkenbach, B., Beicht, P., Claasen, S., Luers, G., Stuermer, C.A., Herzog, V., and Tikkanen, R. (2004). Membrane and raft association of reggie-1/flotillin-2: role of myristoylation, palmitoylation and oligomerization and induction of filopodia by overexpression. Biochem. J.378, 509–518.10.1042/bj20031100Suche in Google Scholar

Ostermeyer, A.G., Paci, J.M., Zeng, Y., Lublin, D.M., Munro, S., and Brown, D.A. (2001). Accumulation of caveolin in the endoplasmic reticulum redirects the protein to lipid storage droplets. J. Cell Biol.152, 1071–1078.10.1083/jcb.152.5.1071Suche in Google Scholar

Parton, R.G. (1996). Caveolae and caveolins. Curr. Opin. Cell Biol.8, 542–548.10.1016/S0955-0674(96)80033-0Suche in Google Scholar

Parton, R.G. (2003). Caveolae – from ultrastructure to molecular mechanisms. Nat. Rev. Mol. Cell Biol.4, 162–167.10.1038/nrm1017Suche in Google Scholar PubMed

Pol, A., Luetterforst, R., Lindsay, M., Heino, S., Ikonen, E., and Parton, R.G. (2001). A caveolin dominant negative mutant associates with lipid bodies and induces intracellular cholesterol imbalance. J. Cell Biol.152, 1057–1070.10.1083/jcb.152.5.1057Suche in Google Scholar PubMed PubMed Central

Pol, A., Martin, S., Fernandez, M.A., Ferguson, C., Carozzi, A., Luetterforst, R., Enrich, C., and Parton, R.G. (2004). Dynamic and regulated association of caveolin with lipid bodies: modulation of lipid body motility and function by a dominant negative mutant. Mol. Biol. Cell15, 99–110.10.1091/mbc.e03-06-0368Suche in Google Scholar PubMed PubMed Central

Pol, A., Martin, S., Fernandez, M.A., Ingelmo-Torres, M., Ferguson, C., Enrich, C., and Parton, R.G. (2005). Cholesterol and fatty acids regulate dynamic caveolin trafficking through the Golgi complex and between the cell Surface and lipid bodies. Mol. Biol. Cell16, 2091–2105.10.1091/mbc.e04-08-0737Suche in Google Scholar

Rajendran, L. and Simons, K. (2005). Lipid rafts and membrane dynamics. J. Cell Sci.118, 1099–1102.10.1242/jcs.01681Suche in Google Scholar

Rajendran, L., Masilamani, M., Solomon, S., Tikkanen, R., Stuermer, C.A., Plattner, H., and Illges, H. (2003). Asymmetric localization of flotillins/reggies in preassembled platforms confers inherent polarity to hematopoietic cells. Proc. Natl. Acad. Sci. USA100, 8241–8246.10.1073/pnas.1331629100Suche in Google Scholar

Rajendran, L., Honsho, M., Zahn, T.R., Keller, P., Geiger, K.D., Verkade, P., and Simons, K. (2006). Alzheimer's disease β- amyloid peptides are released in association with exosomes. Proc. Natl. Acad. Sci. USA103, 11172–11177.10.1073/pnas.0603838103Suche in Google Scholar

Razani, B., Engelman, J.A., Wang, X.B., Schubert, W., Zhang, X.L., Marks, C.B., Macaluso, F., Russell, R.G., Li, M., Pestell, R.G., et al. (2001). Caveolin-1 null mice are viable but show evidence of hyperproliferative and vascular abnormalities. J. Biol. Chem.276, 38121–38138.10.1074/jbc.M105408200Suche in Google Scholar

Schroeder, W.T., Stewart-Galetka, S., Mandavilli, S., Parry, D.A., Goldsmith, L., and Duvic, M. (1994). Cloning and characterization of a novel epidermal cell surface antigen (ESA). J. Biol. Chem.269, 19983–19991.10.1016/S0021-9258(17)32117-8Suche in Google Scholar

Schuck, S., Honsho, M., Ekroos, K., Shevchenko, A., and Simons, K. (2003). Resistance of cell membranes to different detergents. Proc. Natl. Acad. Sci. USA100, 5795–5800.10.1073/pnas.0631579100Suche in Google Scholar PubMed PubMed Central

Schulte, T., Paschke, K.A., Laessing, U., Lottspeich, F., and Stuermer, C.A. (1997). Reggie-1 and reggie-2, two cell surface proteins expressed by retinal ganglion cells during axon regeneration. Development124, 577–587.10.1242/dev.124.2.577Suche in Google Scholar PubMed

Shyng, S.L., Heuser, J.E., and Harris, D.A. (1994). A glycolipid- anchored prion protein is endocytosed via clathrin-coated pits. J. Cell Biol.125, 1239–1250.10.1083/jcb.125.6.1239Suche in Google Scholar PubMed PubMed Central

Simons, K., and Toomre, D. (2000). Lipid rafts and signal transduction. Nat. Rev. Mol. Cell Biol.1, 31–39.10.1038/35036052Suche in Google Scholar PubMed

Simons, K., and Vaz, W.L. (2004). Model systems, lipid rafts, and cell membranes. Annu. Rev. Biophys. Biomol. Struct.33, 269–295.10.1146/annurev.biophys.32.110601.141803Suche in Google Scholar PubMed

Solomon, S., Masilamani, M., Rajendran, L., Bastmeyer, M., Stuermer, C.A., and Illges, H. (2002). The lipid raft microdomain-associated protein reggie-1/flotillin-2 is expressed in human B cells and localized at the plasma membrane and centrosome in PBMCs. Immunobiology205, 108–119.10.1078/0171-2985-00114Suche in Google Scholar PubMed

Souto, R.P., Vallega, G., Wharton, J., Vinten, J., Tranum-Jensen, J., and Pilch, P.F. (2003). Immunopurification and characterization of rat adipocyte caveolae suggest their dissociation from insulin signaling. J. Biol. Chem.278, 18321–18329.10.1074/jbc.M211541200Suche in Google Scholar PubMed

Umlauf, E., Csaszar, E., Moertelmaier, M., Schuetz, G.J., Parton, R.G., and Prohaska, R. (2004). Association of stomatin with lipid bodies. J. Biol. Chem.279, 23699–23709.10.1074/jbc.M310546200Suche in Google Scholar PubMed

Volonte, D., Galbiati, F., Li, S., Nishiyama, K., Okamoto, T., and Lisanti, M.P. (1999). Flotillins/cavatellins are differentially expressed in cells and tissues and form a hetero-oligomeric complex with caveolins in vivo. Characterization and epitope- mapping of a novel flotillin-1 monoclonal antibody probe. J. Biol. Chem.274, 12702–12709.10.1074/jbc.274.18.12702Suche in Google Scholar PubMed

Published Online: 2007-03-05
Published in Print: 2007-03-01

©2007 by Walter de Gruyter Berlin New York

Artikel in diesem Heft

  1. Supplementary material to the paper “Evolutionary selection pressure and family relationships among connexin genes”
  2. Evolutionary selection pressure and family relationships among connexin genes
  3. Characterization of the large subunit of EcoHK31I methyltransferase by structural modeling and mutagenesis
  4. Purification, characterization, and molecular gene cloning of an antifungal protein from Ginkgo biloba seeds
  5. Maximal Ca2+i stimulation of cardiac Na+/Ca2+ exchange requires simultaneous alkalinization and binding of PtdIns-4,5-P2 to the exchanger
  6. A highly conserved protein secreted by the prostate cancer cell line PC-3 is expressed in benign and malignant prostate tissue
  7. Properties and partial purification of sialate-O-acetyltransferase from bovine submandibular glands
  8. Raft association and lipid droplet targeting of flotillins are independent of caveolin
  9. On the presence of C2-ceramide in mammalian tissues: possible relationship to etherphospholipids and phosphorylation by ceramide kinase
  10. Specific inhibition of interleukin-13 activity by a recombinant human single-chain immunoglobulin domain directed against the IL-13 receptor α1 chain
  11. Effects of disease-modifying anti-rheumatic drugs (DMARDs) on the activities of rheumatoid arthritis-associated cathepsins K and S
  12. Compartmentalised expression of meprin in small intestinal mucosa: enhanced expression in lamina propria in coeliac disease
  13. Human dipeptidyl peptidase III acts as a post-proline-cleaving enzyme on endomorphins
  14. Transgenic mouse brains for the evaluation and quality control of BSE tests
Heruntergeladen am 19.12.2025 von https://www.degruyterbrill.com/document/doi/10.1515/BC.2007.034/pdf
Button zum nach oben scrollen