title: Clusterin: full-length protein and one of its chains show opposing effects on cellular lipid accumulation.
abstract: Proteins, made up of either single or multiple chains, are designed to carry out specific biological functions. We found an interesting example of a two-chain protein where administration of one of its chains leads to a diametrically opposite outcome than that reported for the full-length protein. Clusterin is a highly glycosylated protein consisting of two chains, α- and β-clusterin. We have investigated the conformational features, cellular localization, lipid accumulation, in vivo effects and histological changes upon administration of recombinant individual chains of clusterin. We demonstrate that recombinant α- and β-chains exhibit structural and functional differences and differ in their sub-cellular localization. Full-length clusterin is known to lower lipid levels. In contrast, we find that β-chain-treated cells accumulate 2-fold more lipid than controls. Interestingly, α-chain-treated cells do not show such increase. Rabbits injected with β-chain, but not α-chain, show ~40% increase in weight, with adipocyte hypertrophy, liver and kidney steatosis. Many, sometimes contrasting, roles are ascribed to clusterin in obesity, metabolic syndrome and related conditions. Our findings of differential localization and activities of individual chains of clusterin should help in understanding better the roles of clusterin in metabolism.
authors.affiliation: CSIR- Centre for Cellular and Molecular Biology, Hyderabad, 500007, India.
authors.forename: Suvarsha Rao
authors.initials: SR
authors.lastname: Matukumalli
authors.affiliation: CSIR- Centre for Cellular and Molecular Biology, Hyderabad, 500007, India.
authors.forename: Ramakrishna
authors.initials: R
authors.lastname: Tangirala
authors.affiliation: CSIR- Centre for Cellular and Molecular Biology, Hyderabad, 500007, India.
authors.forename: C M
authors.initials: CM
authors.lastname: Rao
mesh_terms: D000818:Animals; D002460:Cell Line; D048430:Cell Shape; D051152:Clusterin / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D050356:Lipid Metabolism; D008297:Male; D051379:Mice; D018832:Molecular Chaperones / Q000378:metabolism; D011817:Rabbits; D013347:Subcellular Fractions / Q000378:metabolism; D013997:Time Factors; D015430:Weight Gain
chemical_list: D051152:Clusterin; D018832:Molecular Chaperones