Spastin (SPASTIN)

Spastin is a highly conserved enzyme belonging to the AAA ATPase family, essential for severing microtubules through ATP hydrolysis, which enables dynamic remodeling of the cytoskeleton[1][2][3][4]. Its severing activity is crucial for neuronal development, axonal transport, endosome trafficking, and membrane remodeling. Spastin exists primarily as two isoforms (M1 and M87), resulting from alternative start sites and splicing, and contains several functional domains: the hydrophobic domain, microtubule-interacting and trafficking domain (MIT), microtubule-binding domain (MTBD), and the AAA domain responsible for hexamer formation and catalytic activity[1][2][4]. Mutations in the SPAST gene encoding spastin are the leading cause of autosomal dominant hereditary spastic paraplegia, a neurodegenerative disease marked by progressive lower limb spasticity due to selective degeneration of corticospinal tract axons[1][2][3][5]. Spastin plays a dual role in both fragmenting microtubules and facilitating their regrowth, with its activity tightly regulated by ATP-dependent oligomerization and substrate recognition[1][2][3]. Although it shares functional similarities with the related severase katanin, spastin has unique domain architecture and cellular roles, particularly in membrane-associated microtubule remodeling[4].

Other names

SPG4 proteinMicrotubule-severing ATPaseHereditary spastic paraplegia type 4 proteinSpastin M1 (isoform)Spastin M87 (isoform)AAA ATPase domain-containing protein

ATPase inhibition or enhancement (theoretical); Modulation of microtubule severing activity (theoretical, as is done for related severases)