Caveolin-1 is enriched in the peroxisomal membrane of rat hepatocytes. 2010

Jannes Woudenberg, and Krzysztof P Rembacz, and Fiona A J van den Heuvel, and Titia E Woudenberg-Vrenken, and Manon Buist-Homan, and Mariska Geuken, and Mark Hoekstra, and Leo E Deelman, and Carlos Enrich, and Rob H Henning, and Han Moshage, and Klaas Nico Faber
Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

Caveolae are a subtype of cholesterol-enriched lipid microdomains/rafts that are routinely detected as vesicles pinching off from the plasma membrane. Caveolin-1 is an essential component of caveolae. Hepatic caveolin-1 plays an important role in liver regeneration and lipid metabolism. Expression of caveolin-1 in hepatocytes is relatively low, and it has been suggested to also reside at other subcellular locations than the plasma membrane. Recently, we found that the peroxisomal membrane contains lipid microdomains. Like caveolin-1, hepatic peroxisomes are involved in lipid metabolism. Here, we analyzed the subcellular location of caveolin-1 in rat hepatocytes. The subcellular location of rat hepatocyte caveolin-1 was analyzed by cell fractionation procedures, immunofluorescence, and immuno-electron microscopy. Green fluorescent protein (GFP)-tagged caveolin-1 was expressed in rat hepatocytes. Lipid rafts were characterized after Triton X-100 or Lubrol WX extraction of purified peroxisomes. Fenofibric acid-dependent regulation of caveolin-1 was analyzed. Peroxisome biogenesis was studied in rat hepatocytes after RNA interference-mediated silencing of caveolin-1 and caveolin-1 knockout mice. Cell fractionation and microscopic analyses reveal that caveolin-1 colocalizes with peroxisomal marker proteins (catalase, the 70 kDa peroxisomal membrane protein PMP70, the adrenoleukodystrophy protein ALDP, Pex14p, and the bile acid-coenzyme A:amino acid N-acyltransferase BAAT) in rat hepatocytes. Artificially expressed GFP-caveolin-1 accumulated in catalase-positive organelles. Peroxisomal caveolin-1 is associated with detergent-resistant microdomains. Caveolin-1 expression is strongly repressed by the peroxisome proliferator-activated receptor-alpha agonist fenofibric acid. Targeting of peroxisomal matrix proteins and peroxisome number and shape were not altered in rat hepatocytes with 70%-80% reduced caveolin-1 levels and in livers of caveolin-1 knockout mice. CONCLUSIONS Caveolin-1 is enriched in peroxisomes of hepatocytes. Caveolin-1 is not required for peroxisome biogenesis, but this unique subcellular location may determine its important role in hepatocyte proliferation and lipid metabolism.

UI MeSH Term Description Entries
D008297 Male Males
D008565 Membrane Proteins Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors. Cell Membrane Protein,Cell Membrane Proteins,Cell Surface Protein,Cell Surface Proteins,Integral Membrane Proteins,Membrane-Associated Protein,Surface Protein,Surface Proteins,Integral Membrane Protein,Membrane Protein,Membrane-Associated Proteins,Membrane Associated Protein,Membrane Associated Proteins,Membrane Protein, Cell,Membrane Protein, Integral,Membrane Proteins, Integral,Protein, Cell Membrane,Protein, Cell Surface,Protein, Integral Membrane,Protein, Membrane,Protein, Membrane-Associated,Protein, Surface,Proteins, Cell Membrane,Proteins, Cell Surface,Proteins, Integral Membrane,Proteins, Membrane,Proteins, Membrane-Associated,Proteins, Surface,Surface Protein, Cell
D011345 Fenofibrate An antilipemic agent which reduces both CHOLESTEROL and TRIGLYCERIDES in the blood. Procetofen,Antara Micronized Procetofen,Apo-Feno-Micro,Apo-Fenofibrate,CiL,Controlip,Fenobeta,Fenofanton,Fenofibrat AL,Fenofibrat AZU,Fenofibrat AbZ,Fenofibrat FPh,Fenofibrat Heumann,Fenofibrat Hexal,Fenofibrat Stada,Fenofibrat-ratiopharm,Fénofibrate Debat,Fénofibrate MSD,Gen-Fenofibrate,LF-178,Lipanthyl,Lipantil,Liparison,Lipidil,Lipidil-Ter,Livesan,Lofibra,MTW-Fenofibrat,Normalip,Novo-Fenofibrate,Nu-Fenofibrate,PMS-Fenofibrate Micro,Phenofibrate,Procetofene,Secalip,Supralip,Tricor,durafenat,fenofibrat von ct,AZU, Fenofibrat,Apo Feno Micro,Apo Fenofibrate,Debat, Fénofibrate,Fenofibrat ratiopharm,Gen Fenofibrate,Heumann, Fenofibrat,Hexal, Fenofibrat,LF 178,LF178,Lipidil Ter,MTW Fenofibrat,Micronized Procetofen, Antara,Novo Fenofibrate,Nu Fenofibrate,PMS Fenofibrate Micro,Procetofen, Antara Micronized,Stada, Fenofibrat
D000074401 Peroxins Proteins that are essential for the assembly of PEROXISOMES. They recognize and transport cytoplasmic proteins that contain PEROXISOMAL TARGETING SIGNALS (PTS) to the peroxisome. Mutations in peroxin (PEX) genes are associated with several PEROXISOMAL DISORDERS. Peroxin,Peroxisome Biogenesis Factors,Biogenesis Factors, Peroxisome
D000217 Acyltransferases Enzymes from the transferase class that catalyze the transfer of acyl groups from donor to acceptor, forming either esters or amides. (From Enzyme Nomenclature 1992) EC 2.3. Acyltransferase
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013347 Subcellular Fractions Components of a cell produced by various separation techniques which, though they disrupt the delicate anatomy of a cell, preserve the structure and physiology of its functioning constituents for biochemical and ultrastructural analysis. (From Alberts et al., Molecular Biology of the Cell, 2d ed, p163) Fraction, Subcellular,Fractions, Subcellular,Subcellular Fraction
D017208 Rats, Wistar A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain. Wistar Rat,Rat, Wistar,Wistar Rats
D051242 Caveolin 1 A tyrosine phosphoprotein that plays an essential role in CAVEOLAE formation. It binds CHOLESTEROL and is involved in LIPIDS transport, membrane traffic, and SIGNAL TRANSDUCTION. Caveolin-1,VIP21 Protein,Vesicular Integral Membrane Protein 21 kDa,alpha-Caveolin,beta-Caveolin,alpha Caveolin,beta Caveolin
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus

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