title: Cytosolic PrP induces apoptosis of cell by disrupting microtubule assembly.
abstract: Prion protein (PrP) is able to bind with tubulin and to interfere with the formation of microtubule. To investigate the influence of accumulation of cytosolic PrP in cytoplasm on microtubule, plasmid pcDNA3.1-PrP23-230 expressing human PrP23-230 was introduced into HeLa cells. Immunoprecipitation assays identified the molecular interaction between cytosolic PrP and cellular tubulin. Confocal microscopy showed the co-localization of the expressed cytosolic PrP with tubulin in cytoplasm. Immunofluorescent assays of tubulin illustrated remarkable disruption of microtubular structures in the cells accumulated with cytosolic PrP. Meanwhile, the expressed cytosolic PrP significantly reduced cell viability and induced cell apoptosis. The amounts of microtubule protein in the cells expressing cytosolic PrP were decreased. Moreover, the levels of endogenous tubulin in the brain tissues of scrapie-infected hamsters were significantly lower than that of normal one. It highlights a close linkage between disruption of microtubule framework and cell death caused by abnormal presence of cellular PrP in cytoplasm. The association of apoptosis with microtubule-disrupting activity caused by cytosolic PrP may further provide insight into the unresolved biological function of PrP in the neurons.
authors.affiliation: State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Ying-Xin Rd 100, Beijing, 100052, People's Republic of China.
authors.forename: Xiao-Li
authors.initials: XL
authors.lastname: Li
authors.forename: Gui-Rong
authors.initials: GR
authors.lastname: Wang
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Jing
authors.forename: Ming-Ming
authors.initials: MM
authors.lastname: Pan
authors.forename: Chen-Fang
authors.initials: CF
authors.lastname: Dong
authors.forename: Rui-Min
authors.initials: RM
authors.lastname: Zhou
authors.forename: Zhao-Yun
authors.initials: ZY
authors.lastname: Wang
authors.forename: Qi
authors.initials: Q
authors.lastname: Shi
authors.forename: Chen
authors.initials: C
authors.lastname: Gao
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Dong
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D006224:Cricetinae; D003600:Cytosol / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008647:Mesocricetus; D008870:Microtubules / Q000378:metabolism*; D011328:Prions / Q000235:genetics / Q000378:metabolism*; D012608:Scrapie / Q000378:metabolism / Q000473:pathology
chemical_list: D011328:Prions