Characterization of drosophila parkin in vivo

Abstract

Parkin, encoding E3 ubiquitin-ligase is linked to Autosomal Recessive Juvenile Parkinsonism (AR-JP). The locomotive defects in Parkinson’s disease patients are known to be due to the selective loss of dopaminergic (DA) neurons. Here, I generated P-element inserted Dparkin null flies with abnormal wing posture and lower climbing ability. Intriguingly, I observed apoptotic phenotypes in Dparkin mutant indirect flight muscle (IFM), including mitochondrial swelling and TUNEL- positive nuclei. Dparkin mutant also showed elaborate branching of motor neurons on IFM. Using GAL4 system, I showed that Dparkin deficiency in DA neurons was responsible for IFM apoptosis. Meanwhile, elaborate neuronal branching, which was alleviated by pan-neuronal expression of exogenous Parkin, failed to be restored by either DA neuronal or muscle expression of exogenous Parkin. Moreover, Dparkin mutant showed reduced pre-synaptic vesicle protein (CSP)-positive signals on IFM, suggesting that Dparkin has a neuronal growth regulatory role at the neuro muscular junction (NMJ) by affecting synaptic transmission. Collectively, I demonstrate that Dparkin has essential roles in both muscle cell survival and motor neuronal branching control, strongly supporting the importance of Parkin in neurodegenerative movement disorder of Parkinson’s disease.