Functional Characterization of Spastin and its Role in Hereditary Spastic Paraplegia

TL;DRAbstract

Hereditary spastic paraplegia (HSP) is a neurodegenerative disease characterized by the spasticity of the lower limbs due to degeneration of the corticospinal tracts. The gene responsible for the most frequent form of autosomal dominant HSP encodes spastin, an ATPase belonging to the AAA family. <br> Studies with specific antibodies indicate that spastin has both a nuclear and cytosolic localization. In human fibroblasts spastin localizes to the PML bodies, but is also present on the centrosome. In HeLa and Cos? cells, during mitosis, spastin is enriched in regions rich in microtubules, like the spindle poles and the midbody. Furthermore, in an immortalized motoneuronal cell line, spastin is detected in the growth cone of the axons. By overexpressing wild-type or ATPase-defective spastin, we show that spastin interacts dynamically with microtubules. This association is mediated by the N-terminal region of the protein and regulated through its ATPase activity. The overexpression of wild

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