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Mammalian acetyl‐CoA carboxylase polymerizes in association with tubulin
Author(s) -
Lee Weissy Michele,
Brownsey Roger William
Publication year - 2008
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.22.1_supplement.807.27
Subject(s) - pyruvate carboxylase , allosteric regulation , tubulin , biochemistry , phosphorylation , microtubule , chemistry , fatty acid synthase , fatty acid , acetyl coa carboxylase , enzyme , biology , microbiology and biotechnology
Acetyl‐CoA carboxylase (ACC) catalyses the formation of malonyl‐CoA, an essential substrate for fatty acid synthase and a potent inhibitor of fatty acid oxidation. Control of ACC activity has important implications for overall energy metabolism and involves complex regulation via gene expression, allosteric mechanisms and multi‐site phosphorylation. A classic characteristic of ACC is allosteric activation by carboxylic acids, leading to the formation of filamentous polymers (up to 5–10‐MDa). Here, we test the hypothesis that ACC polymerization involves additional proteins. ACC polymers were purified by size fractionation and subjected to tandem mass spectrometry to identify associated proteins. Major ACC polymer‐associated proteins included tubulin and fatty acid synthase. The association between ACC and tubulin was validated by co‐immunoprecipitation and confocal microscopy. In reconstitution studies, purified tubulin and/or GTP had no direct effect on catalytic properties of ACC. However, based on immunocytochemical analysis, association with tubulin may be sensitive to the phosphorylation state of ACC. In conclusion, intracellular control of ACC involves complex protein‐protein interactions. These studies were supported by the Canadian Institutes for Health Research and by Scholarships from UBC and the Natural Sciences and Engineering Research Council (WML).