RESEARCH: Advances in understanding Spastin (HSP)

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Human spastin has multiple microtubule-related

functions

Authors: Salinas, Sara1; Carazo-Salas, E.;

Proukakis, Christos; , J. Mark2; Weston, Anne

E.3; Schiavo,

1: Molecular NeuroPathobiology 2: Department of

Clinical Neurosciences, Royal Free and University

College Medical School, London, UK 3: Electron

Microscopy Laboratories, Cancer Research UK London

Research Institute, Lincoln's Inn Fields Laboratories,

London, UK

Hereditary spastic paraplegias (HSPs) are

neurodegenerative diseases caused by mutations in more

than 20 genes, which lead to progressive spasticity

and weakness of the lower limbs. The most frequently

mutated gene causing autosomal dominant HSP is SPG4,

which encodes spastin, a protein that belongs to the

family of ATPases associated with various cellular

activities (AAAs). A number of studies have suggested

that spastin regulates microtubule dynamics. We have

studied the ATPase activity of recombinant human

spastin and examined the effect of taxol-stabilized

microtubules on this activity. We used spastin

translated from the second ATG and provide evidence

that this is the physiologically relevant form. We

showed that microtubules enhance the ATPase activity

of the protein, a property also described for katanin,

an AAA of the same spastin subgroup. Furthermore, we

demonstrated that human spastin has a

microtubule-destabilizing activity and can bundle

microtubules in vitro, providing new insights into the

molecular pathogenesis of HSP.

SOURCE: : Journal of Neurochemistry, Volume 95,

Number 5, December 2005, pp. 1411-1420(10)

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