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Posttranslational modifications within the collagenous domain of adiponectin are required for the formation of its high‐molecular‐weight oligomeric complex
Author(s) -
Xu Aimin,
Wang Yu,
Lam Bo Bo Janice,
Cooper Garth J.S.,
Lam Karen S.L.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a960
Subject(s) - glycosylation , adiponectin , biochemistry , chemistry , lysine , hydroxylation , biology , insulin , enzyme , amino acid , endocrinology , insulin resistance
Adiponectin is an adipocyte‐derived hormone with insulin‐sensitizing and anti‐atherogenic activities. This protein forms three different oligomeric complexes, and each oligomeric form may possess distinct biological functions. Here we investigated the potential roles of the posttranslational modifications in the oligomeric complex formation of adiponectin. Gel filtration chromatography revealed that adiponectin produced from mammalian cells, which possesses proper posttranslational modifications, were able to form high molecular weight (HMW), middle molecular weight (MMW), and low molecular weight (LMW) complexes. Disruption of hydroxylation and glycosylation by substitution of several conserved lysine residues with arginines selectively abrogated the intracellular assembly of the HMW oligomers. Functional studies on adiponectin‐null mice revealed that abrogation of the lysine hydroxylation/glycosylation markedly decreased the ability of adiponectin to activate AMP‐activated protein kinase in the liver tissue, and also attenuated its glucose‐lowering effect. These data suggest that hydroxylation and glycosylation on the lysine residues within the collagen‐like domain of adiponectin is critically involved in regulating the formation of its HMW oligomeric complex, and consequently the biological activities of this metabolic hormone.