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Biochem Biophys Res Commun. 2009 Sep 11;387(1):121-6. doi: 10.1016/j.bbrc.2009.06.138. Epub 2009 Jul 1.

Familial amyotrophic lateral sclerosis-linked mutant SOD1 aberrantly interacts with tubulin.

Author information

1
Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan. kabuta@ncnp.go.jp

Abstract

Mutations in the Cu,Zn-superoxide dismutase (SOD1) gene cause 20-25% of familial amyotrophic lateral sclerosis (ALS). Mutant SOD1 causes motor neuron degeneration through toxic gain-of-function(s). However, the direct molecular targets of mutant SOD1, underlying its toxicity, are not fully understood. In this study, we found that alpha/beta-tubulin is one of the major mutant SOD1-interacting proteins, but that wild-type SOD1 does not interact with it. The interaction between tubulin and mutant SOD1 was detected in the spinal cords of mutant G93A SOD1 transgenic mice before the onset of symptoms. Tubulin interacted with amino acid residues 1-23 and 116-153 of SOD1. Overexpression of mutant SOD1 resulted in the accumulation of tubulin in detergent-insoluble fractions. In a cell-free system, mutant SOD1 modulated tubulin polymerization, while wild-type SOD1 did not. Since tightly regulated microtubule dynamics is essential for neurons to remain viable, alpha/beta-tubulin could be an important direct target of mutant SOD1.

PMID:
19576169
DOI:
10.1016/j.bbrc.2009.06.138
[Indexed for MEDLINE]

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