AMPK γ is Required for Maintaining Epithelial Cell Structure and Polarity

AMP-activated protein kinase (AMPK), a heterotrimeric complex comprising a catalytic α subunit and regulatory β and γ subunits, has been primarily studied as a major metabolic regulator in various organisms, but recent genetic studies discover its novel physiological functions. The first animal model with no functional AMPK γ subunit gene was generated by using Drosophila genetics. AMPK γ null flies demonstrated lethality with severe defects in cuticle formation. Further histological analysis found that deletion of AMPK γ causes severe defects in cell polarity in embryo epithelia. The phosphorylation of nonmuscle myosin regulatory light chain (MRLC), a critical regulator of epithelial cell polarity, was also diminished in AMPK γ null embryo epithelia. These defects in AMPK γ mutant epithelia were successfully restored by over-expression of AMPK γ. Collectively, these results suggested that AMPK γ is a critical cell polarity regulator in metazoan development.