Parkinson's disease (PD) is a heterogenous disease caused by multifactorial etiology. PD is characterized by the loss of dopaminergic (DA) neurons in the substantia nigra and the accumulation of Lewy bodies. In this study, two Drosophila PD models by exposing Drosophila to rotenone (sporadic PD models) are proposed, and the human α-synuclein A30P protein (family PD models) in Drosophila is expressed respectively. Both models recapitulated the main human PD symptoms including the loss of dopaminergic neurons in the brain and severe locomotor deficits. Our study finds that Rotenone induces more serious learning and memory impairment than α-synuclein A30P does.
The characterization and functions of transmembrane protein 59-like(TMEM59L),a type I transmembrane protein,are not clearly understood until now.Some TMEM59L and fluorescent fusion proteins constructs were transfected in cell lines and liposomes,and their localization was observed.The effects of protein constructs were studied by fluorescence microscopy and western blotting.This study reports a novel function of human TMEM59L(hTMEM59L)related to the expression and location of some proteins.In addition,we report two novel splice variants of human TMEM59L(hTMEM59L).The localization of mutants of this protein,lacking a middle region,and a Cterminal deletion,markedly differed from that of full-length hTMEM59L.Intracellular movement assessment in living cells showed the localization of TMEM59L to vesicular structures in the Golgi bodies,and the cell membrane was observed in living cells.Overexpression of TMEM59L markedly increased the level of amyloid precursor protein because of TMEM59L-mediated inhibition of cell membrane transport but did not affect the expression of betasecretase 2.TMEM59L overexpression also significantly increased the levels of Rab GDP dissociation inhibitor alpha and Rab GDP dissociation inhibitor beta proteins.These results suggest that TMEM59L is involved in the packaging of acidic vesicles and thereby functions in the trafficking and processing of intracellular proteins.
