TY - JOUR
T1 - DJ-1 can inhibit microtubule associated protein 1 B formed aggregates
AU - Wang, Zhiquan
AU - Zhang, Yu
AU - Zhang, Shi
AU - Guo, Qianqian
AU - Tan, Yuyan
AU - Wang, Xinyi
AU - Xiong, Ran
AU - Ding, Jianqing
AU - Chen, Shengdi
N1 - Funding Information:
We thank Dr. Jie Shen of Harvard medical school for her kindly providing of the DJ-1 Knock-out Mice. This work was supported by the National Program of Basic Research (2007CB947900, 2010CB945200, 2011CB504104) of China, the Natural Science Fund (30700888, 30770732, 30872729, 30971031), Key Discipline Program of Shanghai Municipality (S30202), Shanghai Key Project of Basic Science Research (10411954500), Shanghai Pujiang Program (08PJ1407900) and Program for Outstanding Medical Academic Leader of Shanghai (LJ 06003).
PY - 2011
Y1 - 2011
N2 - Background: Abnormal accumulation and aggregation of microtubule associated proteins (MAPs) plays an important role in the pathogenesis of neurodegenerative diseases. Loss-of-function mutation of DJ-1/Park7 can cause early onset of PD. DJ-1, a molecular chaperone, can inhibit α-synuclein aggregation. Currently, little is known whether or not loss of function of DJ-1 contributes to abnormal MAPs aggregation in neurodegenerative disorders such as PD. Results: We presented evidence that DJ-1 could bind to microtubule associated protein1b Light Chain (MAP1b-LC). Overexpression of DJ-1 prevented MAP1b-LC aggregation in HEK293t and SH-SY5Y cells while DJ-1 knocking down (KD) enhanced MAP1b-LC aggregation in SH-SY5Y cells. The increase in insoluble MAP1b-LC was also observed in the DJ-1 null mice brain. Moreover, in the DJ-1 KD SH-SY5Y cells, overexpression of MAP1B-LC led to endoplasmic reticulum (ER) stress-induced apoptosis. Conclusion: Our results suggest that DJ-1 acts as a molecular chaperone to inhibit MAP1B aggregation thus leading to neuronal apoptosis. Our study provides a novel insight into the mechanisms that underly the pathogenesis of Parkinson's disease (PD).
AB - Background: Abnormal accumulation and aggregation of microtubule associated proteins (MAPs) plays an important role in the pathogenesis of neurodegenerative diseases. Loss-of-function mutation of DJ-1/Park7 can cause early onset of PD. DJ-1, a molecular chaperone, can inhibit α-synuclein aggregation. Currently, little is known whether or not loss of function of DJ-1 contributes to abnormal MAPs aggregation in neurodegenerative disorders such as PD. Results: We presented evidence that DJ-1 could bind to microtubule associated protein1b Light Chain (MAP1b-LC). Overexpression of DJ-1 prevented MAP1b-LC aggregation in HEK293t and SH-SY5Y cells while DJ-1 knocking down (KD) enhanced MAP1b-LC aggregation in SH-SY5Y cells. The increase in insoluble MAP1b-LC was also observed in the DJ-1 null mice brain. Moreover, in the DJ-1 KD SH-SY5Y cells, overexpression of MAP1B-LC led to endoplasmic reticulum (ER) stress-induced apoptosis. Conclusion: Our results suggest that DJ-1 acts as a molecular chaperone to inhibit MAP1B aggregation thus leading to neuronal apoptosis. Our study provides a novel insight into the mechanisms that underly the pathogenesis of Parkinson's disease (PD).
UR - http://www.scopus.com/inward/record.url?scp=79957901402&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79957901402&partnerID=8YFLogxK
U2 - 10.1186/1750-1326-6-38
DO - 10.1186/1750-1326-6-38
M3 - Article
C2 - 21645326
AN - SCOPUS:79957901402
SN - 1750-1326
VL - 6
JO - Molecular neurodegeneration
JF - Molecular neurodegeneration
IS - 1
M1 - 38
ER -