Alsin, the Product of ALS2 Gene, Suppresses SOD1 Mutant Neurotoxicity through RhoGEF Domain by Interacting with SOD1 Mutants

Kohsuke Kanekura, Yuichi Hashimoto, Takako Niikura, Sadakazu Aiso, Masaaki Matsuoka, Ikuo Nishimoto

Research output: Contribution to journalArticle

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Abstract

Mutation of the ALS2 gene encoding alsin is linked to the onset of autosomal recessive motor neuron diseases, including juvenile-onset amyotrophic lateral sclerosis (ALS). Alsin long form (LF) belongs to the family of the guanine nucleotide exchanging factor (GEF) for small GTPases. Expression of alsin LF, but not alsin short form, protected motor neuronal cells from toxicity induced by mutants of the Cu/Zn-superoxide dismutase (SOD1) gene, which cause autosomal dominant ALS. In contrast, expression of alsin did not suppress neurotoxicity by other neurodegenerative insults such as Alzheimer's disease-related genes. Deletion analysis of alsin LF demonstrated that the RhoGEF domain is essential for alsin-mediated neuroprotection. Furthermore, we found that alsin LF bound to SOD1 mutants, but not to wtSOD1, via the RhoGEF domain. Such functional and physical interaction between two ALS-related genes will become a promising clue to clarify the pathogenesis of ALS and other motor neuron diseases.

Original languageEnglish
Pages (from-to)19247-19256
Number of pages10
JournalJournal of Biological Chemistry
Volume279
Issue number18
DOIs
Publication statusPublished - 2004 Apr 30
Externally publishedYes

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Rho Guanine Nucleotide Exchange Factors
Genes
Neurons
Gene encoding
Guanine Nucleotides
Monomeric GTP-Binding Proteins
Toxicity

ASJC Scopus subject areas

  • Biochemistry

Cite this

Alsin, the Product of ALS2 Gene, Suppresses SOD1 Mutant Neurotoxicity through RhoGEF Domain by Interacting with SOD1 Mutants. / Kanekura, Kohsuke; Hashimoto, Yuichi; Niikura, Takako; Aiso, Sadakazu; Matsuoka, Masaaki; Nishimoto, Ikuo.

In: Journal of Biological Chemistry, Vol. 279, No. 18, 30.04.2004, p. 19247-19256.

Research output: Contribution to journalArticle

Kanekura, Kohsuke ; Hashimoto, Yuichi ; Niikura, Takako ; Aiso, Sadakazu ; Matsuoka, Masaaki ; Nishimoto, Ikuo. / Alsin, the Product of ALS2 Gene, Suppresses SOD1 Mutant Neurotoxicity through RhoGEF Domain by Interacting with SOD1 Mutants. In: Journal of Biological Chemistry. 2004 ; Vol. 279, No. 18. pp. 19247-19256.
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AU - Aiso, Sadakazu

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AU - Nishimoto, Ikuo

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