title: Spastin and microtubules: Functions in health and disease.
abstract: SPG4, the gene encoding for spastin, a member of the ATPases associated with various cellular activities (AAA) family, is mutated in around 40% of cases of autosomal dominant hereditary spastic paraplegia (AD-HSP). This group of neurodegenerative diseases is characterized by a progressive spasticity and lower limb weakness with degeneration of terminal axons in cortico-spinal tracts and dorsal columns. Spastin has two main domains, a microtubule interacting and endosomal trafficking (MIT) domain at the N-terminus and the C-terminus AAA domain. Early studies suggested that spastin interacts with microtubules similarly to katanin, a member of the same subgroup of AAA. Recent evidence confirmed that spastin possesses microtubule-severing activity but can also bundle microtubules in vitro. Understanding the physiologic and pathologic involvement of these activities and their regulation is critical in the study of HSP.
authors.affiliation: Molecular NeuroPathobiology, Cancer Research United Kingdom London Research Institute, Lincoln's Inn Fields Laboratories, London, UK.
authors.forename: Sara
authors.initials: S
authors.lastname: Salinas
authors.forename: Rafael E
authors.initials: RE
authors.lastname: Carazo-Salas
authors.forename: Christos
authors.initials: C
authors.lastname: Proukakis
authors.forename: Giampietro
authors.initials: G
authors.lastname: Schiavo
authors.forename: Thomas T
authors.initials: TT
authors.lastname: Warner
mesh_terms: D000251:Adenosine Triphosphatases / Q000502:physiology*; D000818:Animals; D006801:Humans; D008870:Microtubules / Q000502:physiology*; D019636:Neurodegenerative Diseases / Q000378:metabolism / Q000503:physiopathology*; D000074181:Spastin
chemical_list: D000251:Adenosine Triphosphatases; D000074181:Spastin; C400283:SPAST protein, human