Spastin and microtubules: Functions in health and disease.
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.
Salinas
Sara
S
Molecular NeuroPathobiology, Cancer Research United Kingdom London Research Institute, Lincoln's Inn Fields Laboratories, London, UK.
Carazo-Salas
Rafael E
RE
Proukakis
Christos
C
Schiavo
Giampietro
G
Warner
Thomas T
TT
D000251:Adenosine Triphosphatases / Q000502:physiology*; D000818:Animals; D006801:Humans; D008870:Microtubules / Q000502:physiology*; D019636:Neurodegenerative Diseases / Q000378:metabolism / Q000503:physiopathology*; D000074181:Spastin
D000251:Adenosine Triphosphatases; D000074181:Spastin; C400283:SPAST protein, human