title: Retrograde trafficking of VMAT2 and its role in protein stability in non-neuronal cells.
abstract: Increasing evidence suggests that the impaired neuroprotection of vesicular monoamine transporter 2 (VMAT2) contributes to the pathogenesis of Parkinson's disease. That has been linked to aberrant subcellular retrograde trafficking as strongly indicated by recent genomic studies on familial Parkinson's diseases. However, whether VMAT2 function is regulated by retrograde trafficking is unknown. By using biochemistry and cell biology approaches, we have shown that VMAT2 was stringently localized to the trans-Golgi network and underwent retrograde trafficking in non-neuronal cells. The transporter also interacted with the key component of retromer, Vps35, biochemically and subcellularly. Using specific siRNA, we further showed that Vps35 depletion altered subcellular localization of VMAT2. Moreover, siRNA-mediated Vps35 knockdown also decreased the stability of VMAT2 as demonstrated by the reduced half-life. Thus, our work suggested that altered vesicular trafficking of VMAT2 may play a vital role in neuroprotection of the transporter as well as in the pathogenesis of Parkinson's disease.
authors.affiliation: Department of Physiology, School of Basic Medical Science, Nanjing Medical University, Nanjing, Jiangsu 211166, China.
authors.forename: Qiuzi
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Department of Physiology, School of Basic Medical Science, Nanjing Medical University, Nanjing, Jiangsu 211166, China.
authors.forename: Hongfei
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Physiology, School of Basic Medical Science, Nanjing Medical University, Nanjing, Jiangsu 211166, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Physiology, School of Basic Medical Science, Nanjing Medical University, Nanjing, Jiangsu 211166, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Chang
authors.affiliation: Department of Pharmacology & Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, USA.
authors.forename: Yu
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Physiology, School of Basic Medical Science, Nanjing Medical University, Nanjing, Jiangsu 211166, China.|Department of Pharmacology & Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, USA; yjliu78@njmu.edu.cn.
authors.forename: Yongjian
authors.initials: Y
authors.lastname: Liu
keywords: Parkinson's disease; VMAT2; Vps35; retrograde trafficking