The AAA ATPase spastin links microtubule severing to membrane modelling

In 1999, mutations in the gene encoding the microtubule severing AAA ATPase spastin were identified as a major cause of a genetic neurodegenerative condition termed hereditary spastic paraplegia (HSP). This finding stimulated intense study of the spastin protein and over the last decade, a combinati...

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Bibliographic Details
Published in:Biochimica et biophysica acta Vol. 1823; no. 1; pp. 192 - 197
Main Authors: Lumb, Jennifer H., Connell, James W., Allison, Rachel, Reid, Evan
Format: Journal Article
Language:English
Published: Netherlands Elsevier B.V 01-01-2012
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Summary:In 1999, mutations in the gene encoding the microtubule severing AAA ATPase spastin were identified as a major cause of a genetic neurodegenerative condition termed hereditary spastic paraplegia (HSP). This finding stimulated intense study of the spastin protein and over the last decade, a combination of cell biological, in vivo, in vitro and structural studies have provided important mechanistic insights into the cellular functions of the protein, as well as elucidating cell biological pathways that might be involved in axonal maintenance and degeneration. Roles for spastin have emerged in shaping the endoplasmic reticulum and the abscission stage of cytokinesis, in which spastin appears to couple membrane modelling to microtubule regulation by severing. This article is part of a Special Issue entitled: AAA ATPases: structure and function. ► Spastin is a microtubule severing ATPase and mutations in the gene encoding spastin cause axonal degeneration. ► N‐terminal spastin domains serve to recruit it to cellular sites of action. ► A hydrophobic domain localizes spastin to the endoplasmic reticulum. ► The MIT domain recruits spastin to endosomes and the cytokinetic midbody. ► Spastin regulates microtubules in relation to sites of membrane modelling.
ISSN:0167-4889
0006-3002
1879-2596
DOI:10.1016/j.bbamcr.2011.08.010