Characterization of cyclophilin 40 in drosophila melanogaster

Abstract

Cyclophilin 40 (Cyp40), a 40 kDa cyclosporin A-binding immunophilin first identified in association with inactivated estrogen receptors, appears to have a diverse array of physiological functions. To understand the biological functions of Cyp40 in $\It{Drosophila}$, I generated and characterized gain-of-function and loss-of-function mutants for $\It{dCyp40}$. Overexpression or suppression of $\It{dCyp40}$ exhibited no phenotypes in eyes, wings and thoraxes. The $\It{dCyp40}$ null mutants were viable and fertile, but with reduced lifespan at high temperature whereas overexpression of $\It{dCyp40}$ extended fly longevity at the same condition, suggesting $\It{dCyp40}$ is a heat-responsive protein. Unexpectedly, neither cell cycle arrest nor apoptosis was induced by $\It{dCyp40}$ overexpression or loss-of-function. Moreover, $\It{dCyp40}$ also did not rescue $\It{PINK1^{B9}}$ mutant phenotypes in the wing and thorax. Taken together, using Drosophila system, I have developed invaluable tools to study the physiological functions of Cyp40.