The C-terminus of tau protein plays an important role in its stability and toxicity.
The identification of tau fragments generated by proteolysis in the neurons of AD patients and in neurofibrillary tangles encourages research on the toxicity of truncated tau. However, the detailed mechanism underlying the proteolysis-induced toxicity of tau is not clear and even controversial in some cases. In the present study, we used Drosophila as a model to evaluate the toxicity of a set of truncated tau fragments in vivo and found that the flies harboring C-terminal-truncated tau exhibited less toxicity due to the unstable characteristic of C-terminal-truncated tau fragments. Further study carried out in cultured Drosophila Kc cells revealed that C-terminal-truncated tau fragments degrade faster than full-length tau or N-terminal-truncated fragments. Collectively, our data implicate proteolysis of tau as an important pathway mediating tau degradation and neurotoxicity in vivo.
State Key Laboratory of Cognitive Neuroscience and Learning and IDG/McGovern Institute for Brain Research, College of Life Sciences, Beijing Normal University, Beijing, China.|Center for Collaboration and Innovation in Brain and Learning Sciences, Beijing Normal University, Beijing, China.
Junhua
J
Geng
State Key Laboratory of Cognitive Neuroscience and Learning and IDG/McGovern Institute for Brain Research, College of Life Sciences, Beijing Normal University, Beijing, China.|Center for Collaboration and Innovation in Brain and Learning Sciences, Beijing Normal University, Beijing, China.
Lu
L
Xia
State Key Laboratory of Cognitive Neuroscience and Learning and IDG/McGovern Institute for Brain Research, College of Life Sciences, Beijing Normal University, Beijing, China.|Center for Collaboration and Innovation in Brain and Learning Sciences, Beijing Normal University, Beijing, China.
Wanjie
W
Li
State Key Laboratory of Cognitive Neuroscience and Learning and IDG/McGovern Institute for Brain Research, College of Life Sciences, Beijing Normal University, Beijing, China. douf@bnu.edu.cn.|Center for Collaboration and Innovation in Brain and Learning Sciences, Beijing Normal University, Beijing, China. douf@bnu.edu.cn.|College of Life Sciences, Beijing Normal University, No. 19 Xin Jie Kou Wai Avenue, Beijing, 100875, China. douf@bnu.edu.cn.
Fei
F
Dou
D000818:Animals; D002460:Cell Line; D004330:Drosophila / Q000378:metabolism; D006801:Humans; D010446:Peptide Fragments / Q000378:metabolism / Q000633:toxicity; D055550:Protein Stability; D017434:Protein Structure, Tertiary; D059748:Proteolysis; D016875:tau Proteins / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*
D010446:Peptide Fragments; D016875:tau Proteins