title: The secreted oligomeric form of α-synuclein affects multiple steps of membrane trafficking.
abstract: α-Synuclein (α-syn) can be secreted from neurons into the extracellular space, affecting the homeostasis of neighboring cells, but the pathophysiology of secreted α-syn remains largely unknown. We found that when exogenously applied to COS-7 cells, α-syn secreted from differentiated SH-SY5Y cells was taken up by dynamin-dependent endocytosis. Upon internalization, α-syn significantly increased the rate of transferrin receptor (TfR) internalization and recycling, and subsequently the surface levels of TfR. The effects are attributable to the oligomeric form, but not monomeric or fibrillar form, of extracellular α-syn. Together, multiple alterations in membrane trafficking by secreted oligomeric α-syn may contribute to the early stages of pathogenesis in Parkinson's disease.
authors: Department of Physiology and Biomedical Sciences, Seoul National University College of Medicine, Seoul, South Korea.
authors: Ye-Jin
authors: YJ
authors: Chai
authors: DongKyu
authors: D
authors: Kim
authors: Joohyun
authors: J
authors: Park
authors: Haiyan
authors: H
authors: Zhao
authors: Seung-Jae
authors: SJ
authors: Lee
authors: Sunghoe
authors: S
authors: Chang
mesh_terms: D000818:Animals; D019556:COS Cells; D002460:Cell Line; D002522:Chlorocebus aethiops; D017077:Culture Media, Conditioned / Q000737:chemistry; D034281:Dynamins / Q000378:metabolism; D004705:Endocytosis; D006801:Humans; D007700:Kinetics; D008954:Models, Biological; D058990:Molecular Targeted Therapy; D010300:Parkinson Disease / Q000188:drug therapy; D020836:Protein Structure, Quaternary; D021381:Protein Transport; D011990:Receptors, Transferrin / Q000378:metabolism; D014168:Transferrin / Q000378:metabolism; D051844:alpha-Synuclein / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*
chemical_list: D017077:Culture Media, Conditioned; D011990:Receptors, Transferrin; D014168:Transferrin; D051844:alpha-Synuclein; D034281:Dynamins