Journal article
Novel septin 9 repeat motifs altered in neuralgic amyotrophy bind and bundle microtubules
The Journal of cell biology, v 203(6), pp 895-905
23 Dec 2013
PMID: 24344182
Abstract
Septin 9 (SEPT9) interacts with microtubules (MTs) and is mutated in hereditary neuralgic amyotrophy (HNA), an autosomal-dominant neuropathy. The mechanism of SEPT9 interaction with MTs and the molecular basis of HNA are unknown. Here, we show that the N-terminal domain of SEPT9 contains the novel repeat motifs K/R-x-x-E/D and R/K-R-x-E, which bind and bundle MTs by interacting with the acidic C-terminal tails of β-tubulin. Alanine scanning mutagenesis revealed that the K/R-R/x-x-E/D motifs pair electrostatically with one another and the tails of β-tubulin, enabling septin–septin interactions that link MTs together. SEPT9 isoforms lacking repeat motifs or containing the HNA-linked mutation R88W, which maps to the R/K-R-x-E motif, diminished intracellular MT bundling and impaired asymmetric neurite growth in PC-12 cells. Thus, the SEPT9 repeat motifs bind and bundle MTs, and thereby promote asymmetric neurite growth. These results provide the first insight into the mechanism of septin interaction with MTs and the molecular and cellular basis of HNA.
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Details
- Title
- Novel septin 9 repeat motifs altered in neuralgic amyotrophy bind and bundle microtubules
- Creators
- Xiaobo Bai - Department of Biology, Drexel University, Philadelphia, PA 19104Jonathan R Bowen - Department of Biology, Drexel University, Philadelphia, PA 19104Tara K Knox - Department of Biology, Drexel University, Philadelphia, PA 19104Kaifeng Zhou - Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520Manuela Pendziwiat - Institute of Experimental Medicine, University of Kiel, 24105 Kiel, GermanyGregor Kuhlenbäumer - Institute of Experimental Medicine, University of Kiel, 24105 Kiel, GermanyCharles V Sindelar - Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520Elias T Spiliotis - Department of Biology, Drexel University, Philadelphia, PA 19104
- Publication Details
- The Journal of cell biology, v 203(6), pp 895-905
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biology
- Web of Science ID
- WOS:000329288600004
- Scopus ID
- 2-s2.0-84893817273
- Other Identifier
- 991014878609804721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Cell Biology