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Human spastin has multiple microtubule‐related functions
Author(s) -
Salinas Sara,
CarazoSalas Rafael E.,
Proukakis Christos,
Cooper J. Mark,
Weston Anne E.,
Schiavo Giampietro,
Warner Thomas T.
Publication year - 2005
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2005.03472.x
Subject(s) - microtubule , aaa proteins , microbiology and biotechnology , biology , atpase , biochemistry , enzyme
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 a ssociated with various cellular a ctivities (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.