Gene Symbol: Spast
Description: spastin
Alias: Spg4, spastin, spastic paraplegia 4 (autosomal dominant, spastic paraplegia 4 (autosomal dominant; spastin)
Species: rat
Products:     Spast

Top Publications

  1. Charvin D, Cifuentes Diaz C, Fonknechten N, Joshi V, Hazan J, Melki J, et al. Mutations of SPG4 are responsible for a loss of function of spastin, an abundant neuronal protein localized in the nucleus. Hum Mol Genet. 2003;12:71-8 pubmed
    Mutations of spastin are responsible for the most common autosomal dominant form of hereditary spastic paraplegia (AD-HSP), a disease characterized by axonal degeneration of corticospinal tracts and posterior columns...
  2. Evans K, Gomes E, Reisenweber S, Gundersen G, Lauring B. Linking axonal degeneration to microtubule remodeling by Spastin-mediated microtubule severing. J Cell Biol. 2005;168:599-606 pubmed
    Mutations in the AAA adenosine triphosphatase (ATPase) Spastin (SPG4) cause an autosomal dominant form of hereditary spastic paraplegia, which is a retrograde axonopathy primarily characterized pathologically by the degeneration of long ..
  3. Claudiani P, Riano E, Errico A, Andolfi G, Rugarli E. Spastin subcellular localization is regulated through usage of different translation start sites and active export from the nucleus. Exp Cell Res. 2005;309:358-69 pubmed
    Most cases of autosomal-dominant hereditary spastic paraplegia are linked to mutations in SPG4 encoding spastin, a protein involved in microtubule dynamics and membrane trafficking...
  4. Salinas S, Carazo Salas R, Proukakis C, Cooper J, Weston A, Schiavo G, et al. Human spastin has multiple microtubule-related functions. J Neurochem. 2005;95:1411-20 pubmed
    ..The most frequently mutated gene causing autosomal dominant HSP is SPG4, which encodes spastin, a protein that belongs to the family of ATPases associated with various cellular activities (AAAs)...
  5. White S, Evans K, Lary J, Cole J, Lauring B. Recognition of C-terminal amino acids in tubulin by pore loops in Spastin is important for microtubule severing. J Cell Biol. 2007;176:995-1005 pubmed
    b>Spastin, an AAA ATPase mutated in the neurodegenerative disease hereditary spastic paraplegia, severs microtubules...
  6. Yang D, Rismanchi N, Renvoisé B, Lippincott Schwartz J, Blackstone C, Hurley J. Structural basis for midbody targeting of spastin by the ESCRT-III protein CHMP1B. Nat Struct Mol Biol. 2008;15:1278-86 pubmed publisher
    ..charged multivesicular body protein 1B (CHMP1B) is required for recruitment of the MIT domain-containing protein spastin, a microtubule-severing enzyme, to the midbody. The 2...
  7. Connell J, Lindon C, Luzio J, Reid E. Spastin couples microtubule severing to membrane traffic in completion of cytokinesis and secretion. Traffic. 2009;10:42-56 pubmed publisher
    Mutations in the gene encoding the microtubule (MT)-severing protein spastin are the most common cause of hereditary spastic paraplegia, a genetic condition in which axons of the corticospinal tracts degenerate...
  8. Murmu R, Martin E, Rastetter A, Esteves T, Muriel M, El Hachimi K, et al. Cellular distribution and subcellular localization of spatacsin and spastizin, two proteins involved in hereditary spastic paraplegia. Mol Cell Neurosci. 2011;47:191-202 pubmed publisher
    ..This first study of the endogenous expression of spatacsin and spastizin shows similarities in their expression patterns that could account for their overlapping clinical phenotypes and involvement in a common protein complex. ..
  9. Wen M, Wang C. The nucleotide cycle of spastin correlates with its microtubule-binding properties. FEBS J. 2013;280:3868-77 pubmed publisher
    b>Spastin is an AAA (ATPase associated with diverse cellular activities) protein with microtubule (MT)-severing activity...

More Information


  1. Lacroix B, Van Dijk J, Gold N, Guizetti J, Aldrian Herrada G, Rogowski K, et al. Tubulin polyglutamylation stimulates spastin-mediated microtubule severing. J Cell Biol. 2010;189:945-54 pubmed publisher
    ..In human cells, the generation of long side chains induces spastin-dependent microtubule disassembly and, consistently, only microtubules modified by long glutamate side chains are ..
  2. Goyal U, Renvoisé B, Chang J, Blackstone C. Spastin-interacting protein NA14/SSNA1 functions in cytokinesis and axon development. PLoS ONE. 2014;9:e112428 pubmed publisher
    ..The most frequent form of autosomal dominant HSP results from mutations of the SPG4 gene product spastin. This is an ATPase associated with diverse cellular activities (AAA) protein that binds to and severs ..
  3. Valenstein M, Roll Mecak A. Graded Control of Microtubule Severing by Tubulin Glutamylation. Cell. 2016;164:911-21 pubmed publisher
    ..we find that glutamylation is the main regulator of the hereditary spastic paraplegia microtubule severing enzyme spastin. Glutamylation acts as a rheostat and tunes microtubule severing as a function of glutamate number added per ..
  4. Mead S, Proukakis C, Wood N, Crosby A, Plant G, Warner T. A large family with hereditary spastic paraparesis due to a frame shift mutation of the spastin (SPG4) gene: association with multiple sclerosis in two affected siblings and epilepsy in other affected family members. J Neurol Neurosurg Psychiatry. 2001;71:788-91 pubmed
    ..Genetic analysis of the family has shown linkage to chromosome 2p and sequencing of the spastin gene has identified a 1406delT frameshift mutation in exon 10...
  5. Vietri M, Schink K, Campsteijn C, Wegner C, Schultz S, Christ L, et al. Spastin and ESCRT-III coordinate mitotic spindle disassembly and nuclear envelope sealing. Nature. 2015;522:231-5 pubmed publisher
    ..Subsequent association of another ESCRT-III-like protein, IST1, directly recruits the AAA ATPase spastin to sever microtubules...
  6. Chang J, Lee S, Blackstone C. Protrudin binds atlastins and endoplasmic reticulum-shaping proteins and regulates network formation. Proc Natl Acad Sci U S A. 2013;110:14954-9 pubmed publisher
    ..encoding proteins that function in tubular endoplasmic reticulum (ER) network formation: atlastin-1 (SPG3A), spastin (SPG4), reticulon 2 (SPG12), and receptor expression-enhancing protein 1 (SPG31)...
  7. Guizetti J, Schermelleh L, Mäntler J, Maar S, Poser I, Leonhardt H, et al. Cortical constriction during abscission involves helices of ESCRT-III-dependent filaments. Science. 2011;331:1616-20 pubmed publisher
    ..Simultaneous spastin-mediated removal of underlying microtubules enabled full constriction at the abscission site...
  8. Kasher P, De Vos K, Wharton S, Manser C, Bennett E, Bingley M, et al. Direct evidence for axonal transport defects in a novel mouse model of mutant spastin-induced hereditary spastic paraplegia (HSP) and human HSP patients. J Neurochem. 2009;110:34-44 pubmed publisher
    Mutations in spastin are the most common cause of hereditary spastic paraplegia (HSP) but the mechanisms by which mutant spastin induces disease are not clear...