Gene Symbol: spastin
Description: spastin
Alias: CG5977, D-spastin, Dmel\CG5977, Dspastin, Spas, Spastin, spastin, CG5977-PA, CG5977-PB, CG5977-PC, CG5977-PD, CG5977-PE, CG5977-PF, D-spastin, Dm-Spastin, dspastin, spas-PA, spas-PB, spas-PC, spas-PD, spas-PE, spas-PF, spasin
Species: fruit fly

Top Publications

  1. Brodu V, Baffet A, Le Droguen P, Casanova J, Guichet A. A developmentally regulated two-step process generates a noncentrosomal microtubule network in Drosophila tracheal cells. Dev Cell. 2010;18:790-801 pubmed publisher
    ..MTOC components are first released from the centrosome by the activity of the MT-severing protein Spastin, and then anchored apically through the transmembrane protein Piopio...
  2. Sherwood N, Sun Q, Xue M, Zhang B, Zinn K. Drosophila spastin regulates synaptic microtubule networks and is required for normal motor function. PLoS Biol. 2004;2:e429 pubmed
    ..form of human autosomal dominant hereditary spastic paraplegia (AD-HSP) is caused by mutations in the SPG4 (spastin) gene, which encodes an AAA ATPase closely related in sequence to the microtubule-severing protein Katanin...
  3. Kammermeier L, Spring J, Stierwald M, Burgunder J, Reichert H. Identification of the Drosophila melanogaster homolog of the human spastin gene. Dev Genes Evol. 2003;213:412-5 pubmed
    The human SPG4 locus encodes the spastin gene, which is responsible for the most prevalent form of autosomal dominant hereditary spastic paraplegia (AD-HSP), a neurodegenerative disorder...
  4. Gorfinkiel N, Blanchard G, Adams R, Martinez Arias A. Mechanical control of global cell behaviour during dorsal closure in Drosophila. Development. 2009;136:1889-98 pubmed publisher
    ..Our mutant analysis reveals the contribution of mechanical elements to the rate and pattern of DC. ..
  5. Zhang D, Rogers G, Buster D, Sharp D. Three microtubule severing enzymes contribute to the "Pacman-flux" machinery that moves chromosomes. J Cell Biol. 2007;177:231-42 pubmed Drosophila melanogaster incorporates the activities of three different microtubule severing enzymes, Spastin, Fidgetin, and Katanin...
  6. Roll Mecak A, Vale R. Structural basis of microtubule severing by the hereditary spastic paraplegia protein spastin. Nature. 2008;451:363-7 pubmed publisher
    b>Spastin, the most common locus for mutations in hereditary spastic paraplegias, and katanin are related microtubule-severing AAA ATPases involved in constructing neuronal and non-centrosomal microtubule arrays and in segregating ..
  7. Stramer B, Moreira S, Millard T, Evans I, Huang C, Sabet O, et al. Clasp-mediated microtubule bundling regulates persistent motility and contact repulsion in Drosophila macrophages in vivo. J Cell Biol. 2010;189:681-9 pubmed publisher
    ..align just before cell-cell repulsion, and we show that forcing depolymerization of microtubules by expression of Spastin leads to their defective polarity and failure to contact inhibit from one another...
  8. Du F, Ozdowski E, Kotowski I, Marchuk D, Sherwood N. Functional conservation of human Spastin in a Drosophila model of autosomal dominant-hereditary spastic paraplegia. Hum Mol Genet. 2010;19:1883-96 pubmed publisher
    Mutations in spastin are the most frequent cause of the neurodegenerative disease autosomal dominant-hereditary spastic paraplegia (AD-HSP)...
  9. Van de Bor V, Zimniak G, Cerezo D, Schaub S, Noselli S. Asymmetric localisation of cytokine mRNA is essential for JAK/STAT activation during cell invasiveness. Development. 2011;138:1383-93 pubmed publisher
    ..These findings reveal a novel post-transcriptional regulatory mechanism of JAK/STAT signalling in the control of epithelial cell invasiveness. ..

More Information


  1. Stewart A, Tsubouchi A, Rolls M, Tracey W, Sherwood N. Katanin p60-like1 promotes microtubule growth and terminal dendrite stability in the larval class IV sensory neurons of Drosophila. J Neurosci. 2012;32:11631-42 pubmed publisher
    ..Although loss of the related microtubule-severing protein Spastin also reduces the class IV dendrite arbor, microtubule polymerization within dendrites is unaffected...
  2. Jankovics F, Brunner D. Transiently reorganized microtubules are essential for zippering during dorsal closure in Drosophila melanogaster. Dev Cell. 2006;11:375-85 pubmed
    ..We provide a clearly defined example where cells of a developing organism transiently reorganize their microtubules to fulfill a specialized morphogenetic task. ..
  3. Roll Mecak A, Vale R. The Drosophila homologue of the hereditary spastic paraplegia protein, spastin, severs and disassembles microtubules. Curr Biol. 2005;15:650-5 pubmed
    ..disorders characterized by lower-extremity spasticity and weakness, are most commonly caused by mutations in the spastin gene, which encodes a AAA+ ATPase related to the microtubule-severing protein katanin...
  4. Trotta N, Orso G, Rossetto M, Daga A, Broadie K. The hereditary spastic paraplegia gene, spastin, regulates microtubule stability to modulate synaptic structure and function. Curr Biol. 2004;14:1135-47 pubmed
    ..At neuromuscular junctions (NMJ), Dspastin RNAi causes morphological undergrowth and reduced synaptic area...
  5. Ozdowski E, Gayle S, Bao H, Zhang B, SHERWOOD N. Loss of Drosophila melanogaster p21-activated kinase 3 suppresses defects in synapse structure and function caused by spastin mutations. Genetics. 2011;189:123-35 pubmed publisher
    ..The AAA ATPase Spastin severs microtubules along their lengths and is thought to regulate the balance between long, stable filaments and ..
  6. Orso G, Martinuzzi A, Rossetto M, Sartori E, Feany M, Daga A. Disease-related phenotypes in a Drosophila model of hereditary spastic paraplegia are ameliorated by treatment with vinblastine. J Clin Invest. 2005;115:3026-34 pubmed
    ..Furthermore, its Drosophila homolog, Drosophila spastin (Dspastin), has been recently shown to regulate microtubule stability and synaptic function at the Drosophila larval ..
  7. Julien C, Lissouba A, Madabattula S, Fardghassemi Y, Rosenfelt C, Androschuk A, et al. Conserved pharmacological rescue of hereditary spastic paraplegia-related phenotypes across model organisms. Hum Mol Genet. 2016;25:1088-99 pubmed publisher
    ..We found that locomotor defects found in all of our spastin models could be partially rescued by phenazine, methylene blue, N-acetyl-cysteine, guanabenz and salubrinal...
  8. Mao C, Xiong Y, Xiong Z, Wang Q, Zhang Y, Jin S. Microtubule-severing protein Katanin regulates neuromuscular junction development and dendritic elaboration in Drosophila. Development. 2014;141:1064-74 pubmed publisher
    ..Taken together, our results demonstrate for the first time that Katanin 60 is required for the normal development of neuromuscular synapses and dendrites. ..
  9. Almeida L, Bagnerini P, Habbal A, Noselli S, Serman F. A mathematical model for dorsal closure. J Theor Biol. 2011;268:105-19 pubmed publisher
    ..native setting and also test it further in embryos where the zipping force is perturbed through the expression of spastin (a microtubule severing protein)...
  10. Bulgakova N, Grigoriev I, Yap A, Akhmanova A, Brown N. Dynamic microtubules produce an asymmetric E-cadherin-Bazooka complex to maintain segment boundaries. J Cell Biol. 2013;201:887-901 pubmed publisher
  11. Ye B, Kim J, Yang L, McLachlan I, Younger S, Jan L, et al. Differential regulation of dendritic and axonal development by the novel Krüppel-like factor Dar1. J Neurosci. 2011;31:3309-19 pubmed publisher
    ..that Dar1 promotes dendrite growth in part by suppressing the expression of the microtubule-severing protein Spastin. Our study thus uncovers a novel transcriptional program for microtubule regulation that preferentially controls ..
  12. Baxter S, Allard D, Crowl C, Sherwood N. Cold temperature improves mobility and survival in Drosophila models of autosomal-dominant hereditary spastic paraplegia (AD-HSP). Dis Model Mech. 2014;7:1005-12 pubmed publisher
    ..Over half of AD-HSP cases arise from loss-of-function mutations in spastin, which encodes a microtubule-severing AAA ATPase...
  13. Wang X, Sterne G, Ye B. Regulatory mechanisms underlying the differential growth of dendrites and axons. Neurosci Bull. 2014;30:557-68 pubmed publisher
    ..The knowledge of these underlying molecular mechanisms not only expands our understanding about how neural circuits are wired, but also provides insights that will aid in the rational design of therapies for neurological diseases. ..
  14. Dilks S, Dinardo S. Non-cell-autonomous control of denticle diversity in the Drosophila embryo. Development. 2010;137:1395-404 pubmed publisher
    ..We propose that stripe mediates its effect on hook orientation, in part, via upregulation of shot. ..
  15. Jinushi Nakao S, Arvind R, Amikura R, Kinameri E, Liu A, Moore A. Knot/Collier and cut control different aspects of dendrite cytoskeleton and synergize to define final arbor shape. Neuron. 2007;56:963-78 pubmed
    ..Knot increases dendritic arbor outgrowth through promoting the expression of Spastin, a microtubule-severing protein disrupted in autosomal dominant hereditary spastic paraplegia (AD-HSP)...
  16. Taniguchi K, Hozumi S, Maeda R, Okumura T, Matsuno K. Roles of type I myosins in Drosophila handedness. Fly (Austin). 2007;1:287-90 pubmed
    ..We propose that the actin-based functions of type I Myosins play critical roles in generating LR asymmetry in invertebrates. ..
  17. Myat M, Rashmi R, Manna D, Xu N, Patel U, Galiano M, et al. Drosophila KASH-domain protein Klarsicht regulates microtubule stability and integrin receptor localization during collective cell migration. Dev Biol. 2015;407:103-14 pubmed publisher
    ..cell rearrangement and integrin localization observed in klar mutants could be mimicked by overexpressing Spastin (Spas), a MT severing protein, in otherwise wild-type salivary glands...
  18. Thomas C, Rousset R, Noselli S. JNK signalling influences intracellular trafficking during Drosophila morphogenesis through regulation of the novel target gene Rab30. Dev Biol. 2009;331:250-60 pubmed publisher
    ..We propose that JNK activity upregulates genes involved in intracellular transport in order to provide an increased level of trafficking activity in cells undergoing complex morphogenetic arrangements such as dorsal closure. ..
  19. Ball R, Peled E, Guerrero G, Isacoff E. BMP signaling and microtubule organization regulate synaptic strength. Neuroscience. 2015;291:155-66 pubmed publisher
    ..The spastin mutation, which disorganizes microtubules, disrupted the transmission gradient, supporting this interpretation...
  20. Korey C. We hold these truths to be self-evident, that all flies and men are created equal: Recent progress on human disease models. Fly (Austin). 2007;1:118-22 pubmed
  21. Booth A, Blanchard G, Adams R, Röper K. A dynamic microtubule cytoskeleton directs medial actomyosin function during tube formation. Dev Cell. 2014;29:562-576 pubmed publisher
    ..The medial actomyosin network interacts with the minus ends of acentrosomal microtubule bundles through the cytolinker protein Shot, and disruption of Shot also impairs apical constriction. ..
  22. Jin S, Pan L, Liu Z, Wang Q, Xu Z, Zhang Y. Drosophila Tubulin-specific chaperone E functions at neuromuscular synapses and is required for microtubule network formation. Development. 2009;136:1571-81 pubmed publisher
    ..Genetic analyses revealed an antagonistic interaction between TBCE and the microtubule-severing protein Spastin. Moreover, treatment of muscles with the microtubule-depolymerizing drug nocodazole implicated TBCE as a tubulin ..
  23. Stone M, Rao K, Gheres K, Kim S, Tao J, La Rochelle C, et al. Normal spastin gene dosage is specifically required for axon regeneration. Cell Rep. 2012;2:1340-50 pubmed publisher
    ..We found that axon regeneration is extremely sensitive to levels of the microtubule-severing protein spastin. Although microtubule behavior in uninjured neurons was not perturbed in animals heterozygous for a spastin null ..
  24. Chen G, League G, Nam S. Role of spastin in apical domain control along the rhabdomere elongation in Drosophila photoreceptor. PLoS ONE. 2010;5:e9480 pubmed publisher
    Mutations in spastin are the most common cause of hereditary spastin paraplegia, a neurodegenerative disease. In this study, the role of spastin was examined in Drosophila photoreceptor development...
  25. Guo X, Macleod G, Wellington A, Hu F, Panchumarthi S, Schoenfield M, et al. The GTPase dMiro is required for axonal transport of mitochondria to Drosophila synapses. Neuron. 2005;47:379-93 pubmed
    ..Together, our findings suggest that dMiro is required for controlling anterograde transport of mitochondria and their proper distribution within nerve terminals. ..
  26. Yang N, Inaki M, Cliffe A, Rørth P. Microtubules and Lis-1/NudE/dynein regulate invasive cell-on-cell migration in Drosophila. PLoS ONE. 2012;7:e40632 pubmed publisher
    ..Spatial regulation of cell-cell adhesion may be a common theme, consistent with observing both cell autonomous and non-autonomous requirements in both systems. ..
  27. Chen L, Stone M, Tao J, Rolls M. Axon injury and stress trigger a microtubule-based neuroprotective pathway. Proc Natl Acad Sci U S A. 2012;109:11842-7 pubmed publisher
    ..We conclude that axon injury or stress triggers a microtubule-based neuroprotective pathway that stabilizes neurons against degeneration. ..
  28. Lee M, Paik S, Lee M, Kim Y, Kim S, Nahm M, et al. Drosophila Atlastin regulates the stability of muscle microtubules and is required for synapse development. Dev Biol. 2009;330:250-62 pubmed publisher
    ..We also provide evidence that Atl functions with the microtubule-severing protein Spastin to disassemble microtubules in muscles...
  29. Badano J, Teslovich T, Katsanis N. The centrosome in human genetic disease. Nat Rev Genet. 2005;6:194-205 pubmed
    ..Here, we review the mechanistic relationship between human disease phenotypes and the function of the centrosome, and describe some of the newly-appreciated functions of this organelle in animal cells...
  30. Taniguchi K, Kokuryo A, Imano T, Minami R, Nakagoshi H, Adachi Yamada T. Isoform-specific functions of Mud/NuMA mediate binucleation of Drosophila male accessory gland cells. BMC Dev Biol. 2014;14:46 pubmed publisher
    ..We also propose that Mud(S) is a key regulator triggering cytokinesis skipping in binucleation processes. ..
  31. Meghana C, Ramdas N, Hameed F, Rao M, Shivashankar G, Narasimha M. Integrin adhesion drives the emergent polarization of active cytoskeletal stresses to pattern cell delamination. Proc Natl Acad Sci U S A. 2011;108:9107-12 pubmed publisher
    ..We suggest that differential contributions of adhesion, cytoskeletal, and external stresses must underlie differences in spatial pattern. ..
  32. Gervais L, Casanova J. In vivo coupling of cell elongation and lumen formation in a single cell. Curr Biol. 2010;20:359-66 pubmed publisher
    ..Given the similarities in the formation of fine respiratory tubes and capillaries, we propose that an inward membrane growth model could account for lumen formation in both processes. ..
  33. Rao K, Stone M, Weiner A, Gheres K, Zhou C, Deitcher D, et al. Spastin, atlastin, and ER relocalization are involved in axon but not dendrite regeneration. Mol Biol Cell. 2016;27:3245-3256 pubmed
    Mutations in >50 genes, including spastin and atlastin, lead to hereditary spastic paraplegia (HSP). We previously demonstrated that reduction of spastin leads to a deficit in axon regeneration in a Drosophila model...
  34. Eckert T, Le D, Link S, Friedmann L, Woehlke G. Spastin's microtubule-binding properties and comparison to katanin. PLoS ONE. 2012;7:e50161 pubmed publisher
    b>Spastin and katanin are ring-shaped hexameric AAA ATPases that sever microtubules, and thus crucially depend on a physical interaction with microtubules...
  35. Le Droguen P, Claret S, Guichet A, Brodu V. Microtubule-dependent apical restriction of recycling endosomes sustains adherens junctions during morphogenesis of the Drosophila tracheal system. Development. 2015;142:363-74 pubmed publisher
    ..Altogether, our results uncover an MT-Dynein-dependent apical restriction of recycling endosomes that controls adhesion by sustaining Par-3 and E-Cadherin levels at AJs during morphogenesis. ..
  36. Papadopoulos C, Orso G, Mancuso G, Herholz M, Gumeni S, Tadepalle N, et al. Spastin binds to lipid droplets and affects lipid metabolism. PLoS Genet. 2015;11:e1005149 pubmed publisher
    ..Consistent with these findings, ubiquitous overexpression of Dspastin in Drosophila led to bigger and less numerous LDs in the fat bodies and increased triacylglycerol levels...
  37. Madabattula S, Strautman J, Bysice A, O Sullivan J, Androschuk A, Rosenfelt C, et al. Quantitative Analysis of Climbing Defects in a Drosophila Model of Neurodegenerative Disorders. J Vis Exp. 2015;:e52741 pubmed publisher
    ..The assay is cost effective and does not require extensive training to obtain highly reproducible results. This makes it an excellent technique for screening candidate drugs in Drosophila mutants with locomotion defects. ..
  38. Wang X, Zhang M, Kim J, Macara A, Sterne G, Yang T, et al. The Krüppel-Like Factor Dar1 Determines Multipolar Neuron Morphology. J Neurosci. 2015;35:14251-9 pubmed publisher
  39. Gould R, Brady S. Neuropathology: many paths lead to hereditary spastic paraplegia. Curr Biol. 2004;14:R903-4 pubmed
    ..Studies with animal models are providing new insights into the pathology of hereditary spastic paraplegia, particularly how mutations in multiple, converging pathways can lead to this family of neuropathies. ..