Journal Article

Stathmin, a microtubule-destabilizing protein, is dysregulated in spinal muscular atrophy<sup>†</sup>

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

in Human Molecular Genetics

Volume 19, issue 9, pages 1766-1778
Published in print May 2010 | ISSN: 0964-6906
Published online February 2010 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/ddq058
Stathmin, a microtubule-destabilizing protein, is dysregulated in spinal muscular atrophy†

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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 Smn-knockdown 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.

Journal Article.  6555 words.  Illustrated.

Subjects: Genetics and Genomics

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