X-linked microtubule-associated protein, Mid1, regulates axon development

Lu, Tingjia, Chen, Renchao, Cox, Timothy C., Moldrich, Randal X., Kurniawan, Nyoman, Tan, Guohe, Perry, Jo K., Ashworth, Alan, Bartlett, Perry F., Xu, Li, Zhang, Jing, Lu, Bin, Wu, Mingyue, Shen, Qi, Liu, Yuanyuan, Richards, Linda J. and Xiong, Zhiqi (2013) X-linked microtubule-associated protein, Mid1, regulates axon development. Proceedings of the National Academy of Sciences of the United States of America, 110 47: 19131-19136. doi:10.1073/pnas.1303687110

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Author Lu, Tingjia
Chen, Renchao
Cox, Timothy C.
Moldrich, Randal X.
Kurniawan, Nyoman
Tan, Guohe
Perry, Jo K.
Ashworth, Alan
Bartlett, Perry F.
Xu, Li
Zhang, Jing
Lu, Bin
Wu, Mingyue
Shen, Qi
Liu, Yuanyuan
Richards, Linda J.
Xiong, Zhiqi
Title X-linked microtubule-associated protein, Mid1, regulates axon development
Journal name Proceedings of the National Academy of Sciences of the United States of America   Check publisher's open access policy
ISSN 0027-8424
1091-6490
Publication date 2013-11-19
Year available 2013
Sub-type Article (original research)
DOI 10.1073/pnas.1303687110
Open Access Status File (Author Post-print)
Volume 110
Issue 47
Start page 19131
End page 19136
Total pages 6
Place of publication Washington, DC, United States
Publisher National Academy of Sciences
Language eng
Subject 1000 General
Abstract 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.
Formatted abstract
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.
Keyword Multidisciplinary Sciences
Science & Technology - Other Topics
MULTIDISCIPLINARY SCIENCES
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID 2011CBA00400
30925016
12XD1405500
Institutional Status UQ

 
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