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First published online 30 September 2008
doi: 10.1242/jcs.035220

Journal of Cell Science 121, 3383-3392 (2008)
Published by The Company of Biologists 2008
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Research Article

The protein phosphatase PP2A-B' subunit Widerborst is a negative regulator of cytoplasmic activated Akt and lipid metabolism in Drosophila

Natalia Vereshchagina1,*, Marie-Christine Ramel1,{ddagger},§, Emmanuelle Bitoun2,§ and Clive Wilson1,¶

1 Department of Physiology, Anatomy and Genetics, University of Oxford, Le Gros Clark Building, South Parks Road, Oxford OX1 3QX, UK
2 MRC Functional Genetics Unit, Department of Physiology, Anatomy and Genetics, Oxford Centre for Gene Function, South Parks Road, Oxford OX1 3QX, UK

Author for correspondence (e-mail: clive.wilson{at}dpag.ox.ac.uk)

Accepted 29 July 2008

Inappropriate regulation of the PI3-kinase/PTEN/Akt kinase-signalling cassette, a key downstream target of insulin/insulin-like growth factor signalling (IIS), is associated with several major human diseases such as diabetes, obesity and cancer. In Drosophila, studies have recently revealed that different subcellular pools of activated, phosphorylated Akt can modulate different IIS-dependent processes. For example, a specific pool of activated Akt within the cytoplasm alters aspects of lipid metabolism, a process that is misregulated in both obesity and diabetes. However, it remains unclear how this pool is regulated. Here we show that the protein phosphatase PP2A-B' regulatory subunit Widerborst (Wdb), which coimmunoprecipitates with Akt in vivo, selectively modulates levels of activated Akt in the cytoplasm. It alters lipid droplet size and expression of the lipid storage perilipin-like protein LSD2 in the Drosophila ovary, but not in epithelial cells of the eye imaginal discs. We conclude that isoforms of PP2A-B' can act as subcellular-compartment-specific regulators of PI3-kinase/PTEN/Akt kinase signalling and IIS, potentially providing new targets for modulating individual subcellular pools of activated Akt in insulin-linked disease.

Key words: Insulin, PP2A, Lipid metabolism, Adipose tissue, Akt, Perilipin, Drosophila


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