Stathmin, a microtubule-destabilizing protein, is dysregulated in spinal muscular atrophy

Hsin Lan Wen, Yuan Ta Lin, Chen Hung Ting, Sue Lin-Chao, Hung Li, Hsiu Mei Hsieh-Li

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51 引文 斯高帕斯(Scopus)

摘要

Spinal muscular atrophy (SMA), a motor neuron degeneration disorder, is caused by either mutations or deletions of survival motor neuron 1 (SMN1) gene which result in insufficient SMN protein. Here, we describe a potential link between stathmin and microtubule defects in SMA. Stathmin was identified by screening Smnknockdown NSC34 cells through proteomics analysis. We found that stathmin was aberrantly upregulated in vitro and in vivo, leading to a decreased level of polymerized tubulin, which was correlated with disease severity. Reduced microtubule densities and βIII-tubulin levels in distal axons of affected SMA-like mice and an impaired microtubule network in Smn-deficient cells were observed, suggesting an involvement of stathmin in those microtubule defects. Furthermore, knockdown of stathmin restored the microtubule network defects of Smn-deficient cells, promoted axon outgrowth and reduced the defect in mitochondria transport in SMA-like motor neurons. We conclude that aberrant stathmin levels may play a detrimental role in SMA; this finding suggests a novel approach to treating SMA by enhancing microtubule stability.

原文英語
文章編號ddq058
頁(從 - 到)1766-1778
頁數13
期刊Human molecular genetics
19
發行號9
DOIs
出版狀態已發佈 - 2010 二月 22

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

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