Spastin oligomerizes into a hexamer and the mutant spastin (E442Q) redistribute the wild-type spastin into filamentous microtubule

2008 | journal article. A publication with affiliation to the University of Göttingen.

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​Spastin oligomerizes into a hexamer and the mutant spastin (E442Q) redistribute the wild-type spastin into filamentous microtubule​
Pantakani, D. V. K.; Swapna, L. S.; Srinivasan, N. & Mannan, A. U.​ (2008) 
Journal of Neurochemistry106(2) pp. 613​-624​.​ DOI: https://doi.org/10.1111/j.1471-4159.2008.05414.x 

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Authors
Pantakani, Dasaradha Venkata Krishna; Swapna, Lakshmipuram S.; Srinivasan, Narayanaswamy; Mannan, Ashraf U.
Abstract
Spastin, a member of the ATPases associated with various cellular activities (AAA) family of proteins, is the most frequently mutated in hereditary spastic paraplegia. The defining feature of the AAA proteins is a structurally conserved AAA domain which assembles into an oligomer. By chemical cross-linking and gel filtration chromatography, we show that spastin oligomerizes into a hexamer. Furthermore, to gain a comprehensive overview of the oligomeric structure of spastin, we generated a structural model of the AAA domain of spastin using template structure of VPS4B and p97/VCP. The generated model of spastin provided us with a framework to classify the identified missense mutations in the AAA domain from hereditary spastic paraplegia patients into different structural/functional groups. Finally, through co-localization studies in mammalian cells, we show that E442Q mutant spastin acts in a dominant negative fashion and causes redistribution of both wild-type spastin monomer and spastin interacting protein, RTN1 into filamentous microtubule bundles.
Issue Date
2008
Status
published
Publisher
Blackwell Publishing
Journal
Journal of Neurochemistry 
ISSN
0022-3042

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