Cytosolic PrP induces apoptosis of cell by disrupting microtubule assembly.
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.
Li
Xiao-Li
XL
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.
Wang
Gui-Rong
GR
Jing
Yuan-Yuan
YY
Pan
Ming-Ming
MM
Dong
Chen-Fang
CF
Zhou
Rui-Min
RM
Wang
Zhao-Yun
ZY
Shi
Qi
Q
Gao
Chen
C
Dong
Xiao-Ping
XP
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
D011328:Prions