title: Stathmin, a microtubule-destabilizing protein, is dysregulated in spinal muscular atrophy.
abstract: 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 beta(III)-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.
authors.affiliation: Institute of Molecular Biology, Academia Sinica, Taipei 115, Taiwan.
authors.forename: Hsin-Lan
authors.initials: HL
authors.lastname: Wen
authors.forename: Yuan-Ta
authors.initials: YT
authors.lastname: Lin
authors.forename: Chen-Hung
authors.initials: CH
authors.lastname: Ting
authors.forename: Sue
authors.initials: S
authors.lastname: Lin-Chao
authors.forename: Hung
authors.initials: H
authors.lastname: Li
authors.forename: Hsiu Mei
authors.initials: HM
authors.lastname: Hsieh-Li
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism / Q000473:pathology; D015153:Blotting, Western; D002460:Cell Line; D055785:Gene Knockdown Techniques; D007150:Immunohistochemistry; D051379:Mice; D008854:Microscopy, Electron; D008870:Microtubules / Q000378:metabolism* / Q000473:pathology; D009046:Motor Neurons / Q000378:metabolism* / Q000473:pathology; D009134:Muscular Atrophy, Spinal / Q000378:metabolism* / Q000473:pathology; D009841:Oligonucleotides / Q000235:genetics; D010957:Plasmids / Q000235:genetics; D050777:Stathmin / Q000378:metabolism*; D055533:Survival of Motor Neuron 1 Protein / Q000378:metabolism*
chemical_list: D009841:Oligonucleotides; C526472:Smn1 protein, mouse; D050777:Stathmin; D055533:Survival of Motor Neuron 1 Protein