Tissue-specific downregulation of EDTP suppresses polyglutamine protein aggregates and extends lifespan in Drosophila

Abstract

Drosophila egg-derived tyrosine phosphatase (EDTP, also called JUMPY) is a lipid phosphatase essential in oogenesis and muscle function in the adult stage. Although mammalian JUMPY negatively regulates autophagy, loss-of-JUMPY causes muscle dysfunction and is associated with a rare genetic disorder called centronuclear myopathy. Here we show that tissue-specific downregulation of EDTP in Drosophila non-muscle tissues, particularly glial cells, suppresses the expression of polyglutamine (polyQ) protein aggregates in the same cells and improves survival. Additionally, tissue-specific downregulation of EDTP in glial cells or motoneurons extends lifespan. We demonstrate an approach to fine-tune the expression of a disease-associated gene EDTP for the removal of polyQ protein aggregate and lifespan extension in Drosophila.