Identification of centaurin-α2: a phosphatidylinositide-binding protein present in fat, heart and skeletal muscle

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Summary

We describe here the cloning, expression and characterisation of centaurin-α2 from a rat adipocyte cDNA library. The centaurin-α2 cDNA contains an open reading frame, which codes for a protein of 376 amino acids with predicted mass of 43.5 kDa. Centaurin-α2 shares 51 – 59% identity with centaurin-α1 proteins and has the same domain organisation, consisting of a predicted N-terminal ArfGAP domain followed by two successive pleckstrin homology domains. Despite the sequence similarity, there are a number of notable differences between the previously characterised centaurin-α1 proteins and the newly described centaurin-α2: (i) in vitro lipid binding experiments with centaurin-α2 do not reveal the same selectivity for phosphatidylinositol 3,4,5-trisphosphate over phosphatidylinositol 4,5-bisphosphate that has been shown for centaurin-α1; (ii) unlike centaurin-α1 which is expressed mainly in the brain, centaurin-α2 has a broad tissue distribution, being particularly abundant in fat, heart and skeletal muscle; (iii) in contrast to centaurin-α1 which is found in both membrane and cytosolic fractions, endogenous centaurin-α2 is exclusively present in the dense membrane fractions of cell extracts, suggesting a constitutive membrane association. Insulin stimulation, which stimulates phosphatidylinositol 3,4,5-trisphosphate production, does not alter the subcellular distribution of centaurin-α2 between adipocyte membrane fractions. This observation is consistent with the lack of specificity of centaurin-α2 for phosphatidylinositol 3,4,5-trisphosphate over phosphatidylinositol 4,5-bisphosphate.

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