Identification of a host molecule inportant for prion infection

2014 Fiscal Year Final Research Report

• Project/Area Number: 25670422
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Neurology
• Research Institution: The University of Tokushima
• Principal Investigator: SAKAGUCHI Suehiro 徳島大学, 疾患酵素学研究センター, 教授 (60274635)
• Co-Investigator(Kenkyū-buntansha): HARA Hideyuki 徳島大学, 疾患酵素学研究センター, 助教 (40469953)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: プリオン / ソーチリン / プリオン病 / プリオンタンパク質 / 感受性

Outline of Final Research Achievements

We identified sortilin as a novel PrPC-binding molecule in this study. Sortilin is a transmembrane protein playing an important role in protein trafficking. Immunocytochemical staining revealed that PrPC is colocalized with sortilin mainly on the plasma membrane. Knockdown of sortilin using siRNA caused increase in PrPSc levels in prion-infected mouse neuroblastoma N2a cells. On the contrary, forced overexpression of sortilin reduced PrPSc levels in prion-infected cells. We also established sortilin-knockout N2a cell lines and infected them with prions. Compared to control N2a cells, the knockout cells were highly susceptible to prions and produced much higher levels of PrPSc. These results indicate that sortilin functions to inhibit the conversion of PrPC into PrPSc.

Free Research Field

ウイルス学