TY - JOUR
T1 - X-linked microtubule-associated protein, Mid1, regulates axon development
AU - Lu, Tingjia
AU - Chen, Renchao
AU - Cox, Timothy C.
AU - Moldrich, Randal X.
AU - Kurniawan, Nyoman
AU - Tan, Guohe
AU - Perry, Jo K.
AU - Ashworth, Alan
AU - Bartlett, Perry F.
AU - Xu, Li
AU - Zhang, Jing
AU - Lu, Bin
AU - Wu, Mingyue
AU - Shen, Qi
AU - Liu, Yuanyuan
AU - Richards, Linda J.
AU - Xiong, Zhiqi
N1 - Funding Information:
The authors gratefully acknowledge the financial supports from the National Natural Science Foundation of China (Nos. 51323011, 51236007), the Program for New Century Excellent Talents in University (No. NCET-13-0455), the Natural Science Foundation of Shaanxi Province (No. 2014KW07-02), the Natural Science Foundation of Jiangsu Province (No. BK20141212) and the Nano Research Program of Suzhou City (Nos. ZXG201442, ZXG2013003). S. Shenwas supported by the Foundation for the Author of National Excellent Doctoral Dissertation of China (No. 201335) and the "Fundamental Research Funds for the Central Universities."
PY - 2013/11/19
Y1 - 2013/11/19
N2 - Opitz syndrome (OS) is a genetic neurological disorder. The gene responsible for the X-linked form of OS, Midline-1 (MID1), encodes an E3 ubiquitin ligase that regulates the degradation of the catalytic subunit of protein phosphatase 2A (PP2Ac). However, how Mid1 functions during neural development is largely unknown. In this study, we provide data from in vitro and in vivo experiments suggesting that silencing Mid1 in developing neurons promotes axon growth and branch formation, resulting in a disruption of callosal axon projections in the contralateral cortex. In addition, a similar phenotype of axonal development was observed in the Mid1 knockout mouse. This defect was largely due to the accumulation of PP2Ac in Mid1-depleted cells as further down-regulation of PP2Ac rescued the axonal phenotype. Together, these data demonstrate that Mid1-dependent PP2Ac turnover is important for normal axonal development and that dysregulation of this process may contribute to the underlying cause of OS.
AB - Opitz syndrome (OS) is a genetic neurological disorder. The gene responsible for the X-linked form of OS, Midline-1 (MID1), encodes an E3 ubiquitin ligase that regulates the degradation of the catalytic subunit of protein phosphatase 2A (PP2Ac). However, how Mid1 functions during neural development is largely unknown. In this study, we provide data from in vitro and in vivo experiments suggesting that silencing Mid1 in developing neurons promotes axon growth and branch formation, resulting in a disruption of callosal axon projections in the contralateral cortex. In addition, a similar phenotype of axonal development was observed in the Mid1 knockout mouse. This defect was largely due to the accumulation of PP2Ac in Mid1-depleted cells as further down-regulation of PP2Ac rescued the axonal phenotype. Together, these data demonstrate that Mid1-dependent PP2Ac turnover is important for normal axonal development and that dysregulation of this process may contribute to the underlying cause of OS.
UR - http://www.scopus.com/inward/record.url?scp=84888102925&partnerID=8YFLogxK
U2 - 10.1073/pnas.1303687110
DO - 10.1073/pnas.1303687110
M3 - Article
C2 - 24194544
AN - SCOPUS:84888102925
SN - 0027-8424
VL - 110
SP - 19131
EP - 19136
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 47
ER -