Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 515K) PPT slides of all figures Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Fujimoto, T. Articles by Nomura, R. Search for Related Content PubMed PubMed Citation Articles by Fujimoto, T. Articles by Nomura, R. Social Bookmarking                            What's this?

© The Rockefeller University Press, 0021-9525/2001//1079 $5.00
The Journal of Cell Biology, Volume 152, Number 5, , 2001 1079-1086

Caveolin-2 Is Targeted to Lipid Droplets, a New "Membrane Domain" in the Cell

^a Department of Anatomy and Molecular Cell Biology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan
^b Department of Anatomy, Gunma University School of Medicine, Maebashi 371-8511, Japan
Department of Anatomy and Molecular Cell Biology, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa, Nagoya 466-8550, Japan.81 52-744-201181 52-744-2000

tfujimot{at}med.nagoya-u.ac.jp

Caveolin-1 and -2 constitute a framework of caveolae in nonmuscle cells. In the present study, we showed that caveolin-2, especially its β isoform, is targeted to the surface of lipid droplets (LD) by immunofluorescence and immunoelectron microscopy, and by subcellular fractionation. Brefeldin A treatment induced further accumulation of caveolin-2 along with caveolin-1 in LD. Analysis of mouse caveolin-2 deletion mutants revealed that the central hydrophobic domain (residues 87–119) and the NH₂-terminal (residues 70–86) and COOH-terminal (residues 120–150) hydrophilic domains are all necessary for the localization in LD. The NH₂- and COOH-terminal domains appeared to be related to membrane binding and exit from ER, respectively, implying that caveolin-2 is synthesized and transported to LD as a membrane protein. In conjunction with recent findings that LD contain unesterified cholesterol and raft proteins, the result implies that the LD surface may function as a membrane domain. It also suggests that LD is related to trafficking of lipid molecules mediated by caveolins.

Key Words: lipid droplet • caveolin-2 • caveolin-1 • membrane domain • brefeldin A

© 2001 The Rockefeller University Press

Abbreviations used in this paper: BFA, brefeldin A; EGFP, enhanced green fluorescent protein; LD, lipid droplets; NRK, normal rat kidney; OA, oleic acid.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Facebook

Reddit

Technorati

Twitter

This article has been cited by other articles:

• Hodges, B. D. M., Wu, C. C. (2010). Proteomic insights into an expanded cellular role for cytoplasmic lipid droplets. J. Lipid Res. 51: 262-273 [Abstract] [Full Text]  
• Hinson, E. R., Cresswell, P. (2009). The antiviral protein, viperin, localizes to lipid droplets via its N-terminal amphipathic {alpha}-helix. Proc. Natl. Acad. Sci. USA 106: 20452-20457 [Abstract] [Full Text]  
• Cobbe, N., Marshall, K. M., Rao, S. G., Chang, C.-W., Di Cara, F., Duca, E., Vass, S., Kassan, A., Heck, M. M. S. (2009). The conserved metalloprotease invadolysin localizes to the surface of lipid droplets. J. Cell Sci. 122: 3414-3423 [Abstract] [Full Text]  
• Urahama, Y., Ohsaki, Y., Fujita, Y., Maruyama, S., Yuzawa, Y., Matsuo, S., Fujimoto, T. (2008). Lipid Droplet-Associated Proteins Protect Renal Tubular Cells from Fatty Acid-Induced Apoptosis. Am. J. Pathol. 173: 1286-1294 [Abstract] [Full Text]  
• Lee, C.-J., Lin, H.-R., Liao, C.-L., Lin, Y.-L. (2008). Cholesterol Effectively Blocks Entry of Flavivirus. J. Virol. 82: 6470-6480 [Abstract] [Full Text]  
• Murphy, G. Jr., Rouse, R. L., Polk, W. W., Henk, W. G., Barker, S. A., Boudreaux, M. J., Floyd, Z. E., Penn, A. L. (2008). Combustion-Derived Hydrocarbons Localize to Lipid Droplets in Respiratory Cells. Am. J. Respir. Cell Mol. Bio. 38: 532-540 [Abstract] [Full Text]  
• Muller, G., Wied, S., Walz, N., Jung, C. (2008). Translocation of Glycosylphosphatidylinositol-Anchored Proteins from Plasma Membrane Microdomains to Lipid Droplets in Rat Adipocytes Is Induced by Palmitate, H2O2, and the Sulfonylurea Drug Glimepiride. Mol. Pharmacol. 73: 1513-1529 [Abstract] [Full Text]  
• Accioly, M. T., Pacheco, P., Maya-Monteiro, C. M., Carrossini, N., Robbs, B. K., Oliveira, S. S., Kaufmann, C., Morgado-Diaz, J. A., Bozza, P. T., Viola, J. P.B. (2008). Lipid Bodies Are Reservoirs of Cyclooxygenase-2 and Sites of Prostaglandin-E2 Synthesis in Colon Cancer Cells. Cancer Res. 68: 1732-1740 [Abstract] [Full Text]  
• Langlois, S., Cowan, K. N., Shao, Q., Cowan, B. J., Laird, D. W. (2008). Caveolin-1 and -2 Interact with Connexin43 and Regulate Gap Junctional Intercellular Communication in Keratinocytes. Mol. Biol. Cell 19: 912-928 [Abstract] [Full Text]  
• Pilch, P. F., Souto, R. P., Liu, L., Jedrychowski, M. P., Berg, E. A., Costello, C. E., Gygi, S. P. (2007). Cellular spelunking: exploring adipocyte caveolae. J. Lipid Res. 48: 2103-2111 [Abstract] [Full Text]  
• Bartz, R., Seemann, J., Zehmer, J. K., Serrero, G., Chapman, K. D., Anderson, R. G.W., Liu, P. (2007). Evidence that Mono-ADP-Ribosylation of CtBP1/BARS Regulates Lipid Storage. Mol. Biol. Cell 18: 3015-3025 [Abstract] [Full Text]  
• Tsuiki, E., Fujita, A., Ohsaki, Y., Cheng, J., Irie, T., Yoshikawa, K., Senoo, H., Mishima, K., Kitaoka, T., Fujimoto, T. (2007). All-trans-Retinol Generated by Rhodopsin Photobleaching Induces Rapid Recruitment of TIP47 to Lipid Droplets in the Retinal Pigment Epithelium. IOVS 48: 2858-2867 [Abstract] [Full Text]  
• Fujimoto, Y., Itabe, H., Kinoshita, T., Homma, K. J., Onoduka, J., Mori, M., Yamaguchi, S., Makita, M., Higashi, Y., Yamashita, A., Takano, T. (2007). Involvement of ACSL in local synthesis of neutral lipids in cytoplasmic lipid droplets in human hepatocyte HuH7. J. Lipid Res. 48: 1280-1292 [Abstract] [Full Text]  
• Nagayama, M., Uchida, T., Gohara, K. (2007). Temporal and spatial variations of lipid droplets during adipocyte division and differentiation. J. Lipid Res. 48: 9-18 [Abstract] [Full Text]  
• Robenek, H., Hofnagel, O., Buers, I., Robenek, M. J., Troyer, D., Severs, N. J. (2006). Adipophilin-enriched domains in the ER membrane are sites of lipid droplet biogenesis. J. Cell Sci. 119: 4215-4224 [Abstract] [Full Text]  
• Boulant, S., Montserret, R., Hope, R. G., Ratinier, M., Targett-Adams, P., Lavergne, J.-P., Penin, F., McLauchlan, J. (2006). Structural Determinants That Target the Hepatitis C Virus Core Protein to Lipid Droplets. J. Biol. Chem. 281: 22236-22247 [Abstract] [Full Text]  
• Frank, P. G., Cheung, M. W.-C., Pavlides, S., Llaverias, G., Park, D. S., Lisanti, M. P. (2006). Caveolin-1 and regulation of cellular cholesterol homeostasis. Am. J. Physiol. Heart Circ. Physiol. 291: H677-H686 [Abstract] [Full Text]  
• Andersson, L., Bostrom, P., Ericson, J., Rutberg, M., Magnusson, B., Marchesan, D., Ruiz, M., Asp, L., Huang, P., Frohman, M. A., Boren, J., Olofsson, S.-O. (2006). PLD1 and ERK2 regulate cytosolic lipid droplet formation. J. Cell Sci. 119: 2246-2257 [Abstract] [Full Text]  
• Ohsaki, Y., Cheng, J., Fujita, A., Tokumoto, T., Fujimoto, T. (2006). Cytoplasmic Lipid Droplets Are Sites of Convergence of Proteasomal and Autophagic Degradation of Apolipoprotein B. Mol. Biol. Cell 17: 2674-2683 [Abstract] [Full Text]  
• Moore, H.-P. H., Silver, R. B., Mottillo, E. P., Bernlohr, D. A., Granneman, J. G. (2005). Perilipin Targets a Novel Pool of Lipid Droplets for Lipolytic Attack by Hormone-sensitive Lipase. J. Biol. Chem. 280: 43109-43120 [Abstract] [Full Text]  
• Manninen, A., Verkade, P., Le Lay, S., Torkko, J., Kasper, M., Fullekrug, J., Simons, K. (2005). Caveolin-1 Is Not Essential for Biosynthetic Apical Membrane Transport. Mol. Cell. Biol. 25: 10087-10096 [Abstract] [Full Text]  
• Gillot, I., Jehl-Pietri, C., Gounon, P., Luquet, S., Rassoulzadegan, M., Grimaldi, P., Vidal, F. (2005). Germ cells and fatty acids induce translocation of CD36 scavenger receptor to the plasma membrane of Sertoli cells. J. Cell Sci. 118: 3027-3035 [Abstract] [Full Text]  
• Ozeki, S., Cheng, J., Tauchi-Sato, K., Hatano, N., Taniguchi, H., Fujimoto, T. (2005). Rab18 localizes to lipid droplets and induces their close apposition to the endoplasmic reticulum-derived membrane. J. Cell Sci. 118: 2601-2611 [Abstract] [Full Text]  
• Robenek, H., Robenek, M. J., Troyer, D. (2005). PAT family proteins pervade lipid droplet cores. J. Lipid Res. 46: 1331-1338 [Abstract] [Full Text]  
• Pol, A., Martin, S., Fernandez, M. A., Ingelmo-Torres, M., Ferguson, C., Enrich, C., 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. Cell 16: 2091-2105 [Abstract] [Full Text]  
• Brasaemle, D. L., Dolios, G., Shapiro, L., 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 [Abstract] [Full Text]  
• Subramanian, V., Garcia, A., Sekowski, A., Brasaemle, D. L. (2004). Hydrophobic sequences target and anchor perilipin A to lipid droplets. J. Lipid Res. 45: 1983-1991 [Abstract] [Full Text]  
• Llorente, A., de Marco, M. C., Alonso, M. A. (2004). Caveolin-1 and MAL are located on prostasomes secreted by the prostate cancer PC-3 cell line. J. Cell Sci. 117: 5343-5351 [Abstract] [Full Text]  
• Cohen, A. W., Hnasko, R., Schubert, W., Lisanti, M. P. (2004). Role of Caveolae and Caveolins in Health and Disease. Physiol. Rev. 84: 1341-1379 [Abstract] [Full Text]  
• Imanishi, Y., Gerke, V., Palczewski, K. (2004). Retinosomes: new insights into intracellular managing of hydrophobic substances in lipid bodies. JCB 166: 447-453 [Abstract] [Full Text]  
• Umlauf, E., Csaszar, E., Moertelmaier, M., Schuetz, G. J., Parton, R. G., Prohaska, R. (2004). Association of Stomatin with Lipid Bodies. J. Biol. Chem. 279: 23699-23709 [Abstract] [Full Text]  
• Cohen, A. W., Razani, B., Schubert, W., Williams, T. M., Wang, X. B., Iyengar, P., Brasaemle, D. L., Scherer, P. E., Lisanti, M. P. (2004). Role of Caveolin-1 in the Modulation of Lipolysis and Lipid Droplet Formation. Diabetes 53: 1261-1270 [Abstract] [Full Text]  
• Palacpac, N. M. Q., Hiramine, Y., Mi-ichi, F., Torii, M., Kita, K., Hiramatsu, R., Horii, T., Mitamura, T. (2004). Developmental-stage-specific triacylglycerol biosynthesis, degradation and trafficking as lipid bodies in Plasmodium falciparum-infected erythrocytes. J. Cell Sci. 117: 1469-1480 [Abstract] [Full Text]  
• Herrera, V. L.M., Didishvili, T., Lopez, L. V., Myers, R. H., Ruiz-Opazo, N. (2004). Genome-Wide Scan Identifies Novel QTLs for Cholesterol and LDL Levels in F2[Dahl RxS]-Intercross Rats. Circ. Res. 94: 446-452 [Abstract] [Full Text]  
• Larigauderie, G., Furman, C., Jaye, M., Lasselin, C., Copin, C., Fruchart, J.-C., Castro, G., Rouis, M. (2004). Adipophilin Enhances Lipid Accumulation and Prevents Lipid Efflux From THP-1 Macrophages: Potential Role in Atherogenesis. Arterioscler. Thromb. Vasc. Bio. 24: 504-510 [Abstract] [Full Text]  
• Kamisaka, Y., Noda, N., Yamaoka, M. (2004). Appearance of Smaller Lipid Bodies and Protein Kinase Activation in the Lipid Body Fraction Are Induced by an Increase in the Nitrogen Source in the Mortierella Fungus. J Biochem 135: 269-276 [Abstract] [Full Text]  
• Ostermeyer, A. G., Ramcharan, L. T., Zeng, Y., Lublin, D. M., Brown, D. A. (2004). Role of the hydrophobic domain in targeting caveolin-1 to lipid droplets. JCB 164: 69-78 [Abstract] [Full Text]  
• Pol, A., Martin, S., Fernandez, M. A., Ferguson, C., Carozzi, A., Luetterforst, R., Enrich, C., 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. Cell 15: 99-110 [Abstract] [Full Text]  
• Hnasko, R., Lisanti, M. P. (2003). The Biology of Caveolae: Lessons from Caveolin Knockout Mice and Implications for Human Disease. Mol. Interv. 3: 445-464 [Abstract] [Full Text]  
• Nan, X., Cheng, J.-X., Xie, X. S. (2003). Vibrational imaging of lipid droplets in live fibroblast cells with coherent anti-Stokes Raman scattering microscopy. J. Lipid Res. 44: 2202-2208 [Abstract] [Full Text]  
• Hansen, G H, Niels-Christiansen, L-L, Immerdal, L, Danielsen, E M (2003). Scavenger receptor class B type I (SR-BI) in pig enterocytes: trafficking from the brush border to lipid droplets during fat absorption. Gut 52: 1424-1431 [Abstract] [Full Text]  
• Dagher, G., Donne, N., Klein, C., Ferre, P., Dugail, I. (2003). HDL-mediated cholesterol uptake and targeting to lipid droplets in adipocytes. J. Lipid Res. 44: 1811-1820 [Abstract] [Full Text]  
• Ohashi, M., Mizushima, N., Kabeya, Y., Yoshimori, T. (2003). Localization of Mammalian NAD(P)H Steroid Dehydrogenase-like Protein on Lipid Droplets. J. Biol. Chem. 278: 36819-36829 [Abstract] [Full Text]  
• Hayashi, T., Su, T.-P. (2003). {sigma}-1 Receptors ({sigma}1 Binding Sites) Form Raft-Like Microdomains and Target Lipid Droplets on the Endoplasmic Reticulum: Roles in Endoplasmic Reticulum Lipid Compartmentalization and Export. J. Pharmacol. Exp. Ther. 306: 718-725 [Abstract] [Full Text]  
• Marchesan, D., Rutberg, M., Andersson, L., Asp, L., Larsson, T., Boren, J., Johansson, B. R., Olofsson, S.-O. (2003). A Phospholipase D-dependent Process Forms Lipid Droplets Containing Caveolin, Adipocyte Differentiation-related Protein, and Vimentin in a Cell-free System. J. Biol. Chem. 278: 27293-27300 [Abstract] [Full Text]  
• DiDonato, D., Brasaemle, D. L. (2003). Fixation Methods for the Study of Lipid Droplets by Immunofluorescence Microscopy. J. Histochem. Cytochem. 51: 773-780 [Abstract] [Full Text]  
• Souto, R. P., Vallega, G., Wharton, J., Vinten, J., Tranum-Jensen, J., Pilch, P. F. (2003). Immunopurification and Characterization of Rat Adipocyte Caveolae Suggest Their Dissociation from Insulin Signaling. J. Biol. Chem. 278: 18321-18329 [Abstract] [Full Text]  
• Shi, S. T., Lee, K.-J., Aizaki, H., Hwang, S. B., Lai, M. M. C. (2003). Hepatitis C Virus RNA Replication Occurs on a Detergent-Resistant Membrane That Cofractionates with Caveolin-2. J. Virol. 77: 4160-4168 [Abstract] [Full Text]  
• Qin, M., Zeng, Z., Zheng, J., Shah, P. K., Schwartz, S. M., Adams, L. D., Sharifi, B. G. (2003). Suppression Subtractive Hybridization Identifies Distinctive Expression Markers for Coronary and Internal Mammary Arteries. Arterioscler. Thromb. Vasc. Bio. 23: 425-433 [Abstract] [Full Text]  
• Garcia, A., Sekowski, A., Subramanian, V., Brasaemle, D. L. (2003). The Central Domain Is Required to Target and Anchor Perilipin A to Lipid Droplets. J. Biol. Chem. 278: 625-635 [Abstract] [Full Text]  
• Gargalovic, P., Dory, L. (2003). Caveolins and macrophage lipid metabolism. J. Lipid Res. 44: 11-21 [Abstract] [Full Text]  
• Tauchi-Sato, K., Ozeki, S., Houjou, T., Taguchi, R., Fujimoto, T. (2002). The Surface of Lipid Droplets Is a Phospholipid Monolayer with a Unique Fatty Acid Composition. J. Biol. Chem. 277: 44507-44512 [Abstract] [Full Text]  
• Razani, B., Woodman, S. E., Lisanti, M. P. (2002). Caveolae: From Cell Biology to Animal Physiology. Pharmacol. Rev. 54: 431-467 [Abstract] [Full Text]  
• Miura, S., Gan, J.-W., Brzostowski, J., Parisi, M. J., Schultz, C. J., Londos, C., Oliver, B., Kimmel, A. R. (2002). Functional Conservation for Lipid Storage Droplet Association among Perilipin, ADRP, and TIP47 (PAT)-related Proteins in Mammals, Drosophila, and Dictyostelium. J. Biol. Chem. 277: 32253-32257 [Abstract] [Full Text]  
• Razani, B., Wang, X. B., Engelman, J. A., Battista, M., Lagaud, G., Zhang, X. L., Kneitz, B., Hou, H. Jr., Christ, G. J., Edelmann, W., Lisanti, M. P. (2002). Caveolin-2-Deficient Mice Show Evidence of Severe Pulmonary Dysfunction without Disruption of Caveolae. Mol. Cell. Biol. 22: 2329-2344 [Abstract] [Full Text]  
• Hope, R. G., Murphy, D. J., McLauchlan, J. (2002). The Domains Required to Direct Core Proteins of Hepatitis C Virus and GB Virus-B to Lipid Droplets Share Common Features with Plant Oleosin Proteins. J. Biol. Chem. 277: 4261-4270 [Abstract] [Full Text]  
• Breuza, L., Corby, S., Arsanto, J.-P., Delgrossi, M.-H., Scheiffele, P., 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 [Abstract] [Full Text]  
• Thomsen, P., Roepstorff, K., Stahlhut, M., van Deurs, B. (2002). Caveolae Are Highly Immobile Plasma Membrane Microdomains, Which Are not Involved in Constitutive Endocytic Trafficking. Mol. Biol. Cell 13: 238-250 [Abstract] [Full Text]  
• Park, D. S., Lee, H., Riedel, C., Hulit, J., Scherer, P. E., Pestell, R. G., Lisanti, M. P. (2001). Prolactin Negatively Regulates Caveolin-1 Gene Expression in the Mammary Gland during Lactation, via a Ras-dependent Mechanism. J. Biol. Chem. 276: 48389-48397 [Abstract] [Full Text]  
• van Meer, G. (2001). Caveolin, Cholesterol, and Lipid Droplets?. JCB 152: F29-F34 [Full Text]  
• Razani, B., Combs, T. P., Wang, X. B., Frank, P. G., Park, D. S., Russell, R. G., Li, M., Tang, B., Jelicks, L. A., Scherer, P. E., Lisanti, M. P. (2002). Caveolin-1-deficient Mice Are Lean, Resistant to Diet-induced Obesity, and Show Hypertriglyceridemia with Adipocyte Abnormalities. J. Biol. Chem. 277: 8635-8647 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents