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

Tingjia Lu, Renchao Chen, Timothy C. Cox, Randal X. Moldrich, Nyoman Kurniawan, Guohe Tan, Jo K. Perry, Alan Ashworth, Perry F. Bartlett, Li Xu, Jing Zhang, Bin Lu, Mingyue Wu, Qi Shen, Yuanyuan Liu, Linda J. Richards, Zhiqi Xiong

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

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.

Original languageEnglish
Pages (from-to)19131-19136
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number47
DOIs
StatePublished - Nov 19 2013

Fingerprint

Dive into the research topics of 'X-linked microtubule-associated protein, Mid1, regulates axon development'. Together they form a unique fingerprint.

Cite this