The involvement of cellular prion protein in the autophagy pathway in neuronal cells.
Apoptosis and autophagy are main mechanisms of neuronal death involved in prion diseases. Serum deprivation can induce both pathways to cell death in various types of cells. To investigate whether PrP(C) is involved in autophagy pathway, we analyzed the level of microtubule-associated protein 1 light chain 3 (LC3), an autophagy marker, by monitoring the conversion from LC3-I into LC3-II in Zürich I Prnp(-/-) hippocampal neuronal cells. We found that the expression level of LC3-II was increased in Prnp(-/-) compared to wild-type cells under serum deprivation. In electron microscopy, increased accumulation of autophagosomes in Prnp(-/-) cells was correlated with the increase in levels of LC3-II. Interestingly, this up-regulated autophagic activity was retarded by the introduction of PrP(C) into Prnp(-/-) cells but not by the introduction of PrP(C) lacking octapeptide repeat region. Thus, the octapeptide repeat region of PrP(C) may play a pivotal role in the control of autophagy exhibited by PrP(C) in neuronal cells.
Oh
Jae-Min
JM
Ilsong Institute of Life Science, Hallym University, Dongan-gu, Anyang, Gyeonggi-do 431-060, Republic of Korea.
Shin
Hae-Young
HY
Park
Seok-Joo
SJ
Kim
Boe-Hyun
BH
Choi
Jin-Kyu
JK
Choi
Eun-Kyoung
EK
Carp
Richard I
RI
Kim
Yong-Sun
YS
D000704:Analysis of Variance; D000818:Animals; D001343:Autophagy; D053148:Caspase 3 / Q000378:metabolism; D002470:Cell Survival / Q000235:genetics; D002478:Cells, Cultured; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission / Q000379:methods; D016253:Microscopy, Immunoelectron / Q000379:methods; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009474:Neurons / Q000502:physiology* / Q000648:ultrastructure; D018621:PrPC Proteins / Q000378:metabolism; D000072002:Prion Proteins; D011328:Prions / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D020449:Repetitive Sequences, Amino Acid; D044967:Serum / Q000378:metabolism; D013997:Time Factors; D014162:Transfection; D015854:Up-Regulation / Q000502:physiology
C480860:Map1lc3b protein, mouse; D008869:Microtubule-Associated Proteins; D018621:PrPC Proteins; D000072002:Prion Proteins; D011328:Prions; C512657:Prnp protein, mouse; D053148:Caspase 3