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Retrograde Transport by Clathrin-Coated Vesicles is Involved in Intracellular Transport of PrPSc in Persistently Prion-Infected Cells

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Title: Retrograde Transport by Clathrin-Coated Vesicles is Involved in Intracellular Transport of PrPSc in Persistently Prion-Infected Cells
Authors: Yamasaki, Takeshi Browse this author
Suzuki, Akio Browse this author
Hasebe, Rie Browse this author →KAKEN DB
Horiuchi, Motohiro Browse this author →KAKEN DB
Issue Date: 16-Aug-2018
Publisher: Nature Publishing Group
Journal Title: Scientific reports
Volume: 8
Start Page: 12241
Publisher DOI: 10.1038/s41598-018-30775-1
Abstract: Intracellular dynamics of an abnormal isoform of prion protein (PrPSc) are tightly associated with prion propagation. However, the machineries involved in the intracellular trafficking of PrPSc are not fully understood. Our previous study suggested that PrPSc in persistently prion-infected cells dynamically circulates between endocytic-recycling compartments (ERCs) and peripheral regions of the cells. To investigate these machineries, we focused on retrograde transport from endosomes to the transGolgi network, which is one of the pathways involved in recycling of molecules. PrPSc was co-localized with components of clathrin-coated vesicles (CCVs) as well as those of the retromer complex, which are known as machineries for retrograde transport. Fractionation of intracellular compartments by density gradient centrifugation showed the presence of PrPSc and the components of CCVs in the same fractions. Furthermore, PrPSc was detected in CCVs isolated from intracellular compartments of prioninfected cells. Knockdown of clathrin interactor 1, which is one of the clathrin adaptor proteins involved in retrograde transport, did not change the amount of PrPSc, but it altered the distribution of PrPSc from ERCs to peripheral regions, including late endosomes/lysosomes. These data demonstrated that some PrPSc is transported from endosomes to ERCs by CCVs, which might be involved in the recycling of PrPSc.
Type: article
Appears in Collections:国際連携研究教育局 : GI-CoRE (Global Institution for Collaborative Research and Education : GI-CoRE) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 堀内 基広

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