Annual Drosophila Research Conference edition:48 pages:951c-951c
48th Annual Drosophila Research Conference edition:48 location:Philadelphia date:01/03/2007
AMP-activated protein kinase (AMPK) is an evolutionarily conserved heterotrimeric serine/threonine kinase. Reacting to changes in cellular energy levels, as reflected in the AMP/ATP ratio, AMPK modulates the activity of a number of cellular metabolic enzymes. Its pivotal role in the control of cellular energy metabolism has been extensively documented in mammals. However, its role in other cellular, developmental or physiological processes is much less well understood. We identified a P-element mutation in CG8057 (alicorn (alc) ), encoding the beta-subunit of AMPK, in a quantitative forward genetic screen for bristle number defects (Norga K et al, Curr Biol. 2003;13:1388-96). The beta-subunit is thought to act as a scaffold for the catalytic alpha-subunit and the regulatory gamma-subunit. To further investigate its function we generated a null mutation by imprecise P-element excision. We also identified allelism with an existing EMS mutant. alc null mutants exhibit mortality at a range of developmental stages (from embryo to early pupa). alc transcripts are widely expressed throughout development. Clonal analysis using the ey-FLP system reveals progressive degeneration of the optic lobe and the antennae. We also observe severe defects in phototaxis and negative geotaxis. Retinal sections show extensive vacuolization, disorganization of ommatidial architecture, photoreceptor loss and vesicular accumulations in the pigment cells. Others have previously also reported neurodegeneration in the gamma-subunit mutant loechrig (loe) (Tschape JA et al, EMBO J 2002; 21:6367-76). AMPK has thus an essential role during development and in functioning of the nervous system in Drosophila. The ongoing study is aimed at elucidating the underlying mechanisms and at determining whether there is a relationship with the role of AMPK in the control of cellular energy metabolism.