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Severing enzymes amplify microtubule arrays through lattice GTP-tubulin incorporation

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Vemu, Annapurna, Szczesna, Ewa, Zehr, Elena A., Spector, Jeffrey O., Grigorieff, Nikolaus, Deaconescu, Alexandra M., Roll-Mecak, Antonina·2018·Science
DOI 10.1126/science.aau1504PMC PMC6510489
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Abstract

Severing to build microtubules: Microtubules are essential intracellular polymers, built from tubulin subunits, that establish cell shape, move organelles, and segregate chromosomes during cell division. Vemu et al. show that microtubule-severing enzymes extract tubulin subunits along the microtubule shaft. This nanoscale damage is repaired by the incorporation of free tubulin, which stabilizes the microtubule against depolymerization. When extraction outpaces repair, microtubules are severed, emerging with stabilized ends composed of fresh tubulin. The severed microtubules act as templates for new microtubule growth, leading to amplification of microtubule number and mass. Thus, seemingly paradoxically, severing enzymes can increase microtubule mass in processes such as neurogenesis and mitotic spindle assembly. Science , this issue p. eaau1504

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  • Such regional variation is consistent with previous studies and suggests that lattice conformation can be locally influenced by lattice-binding microtubule-associated proteins, post-translational modifications, mechanical stress, or repair processes.

    “Such regional variation is consistent with previous studies58and suggest that lattice conformation can be locally influenced by lattice-binding microtuble-associated proteins (MAPs)59–61, post-translational modifications, mechanical stress50,51, or repair processes62–66.”

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  1. [1]Roll-Mecak A, McNally FJ, Microtubule-severing enzymes. Current opinion in cell biology 22, 96– 103 (2010). 19963362 PMC2822099
  2. [2]Sherwood NT, Sun Q, Xue M, Zhang B, Zinn K, Drosophila spastin regulates synaptic microtubule networks and is required for normal motor function. PLoS Biol 2, e429 (2004). 15562320 PMC532392
  3. [3]Trotta N, Orso G, Rossetto MG, Daga A, Broadie K, The hereditary spastic paraplegia gene, spastin, regulates microtubule stability to modulate synaptic structure and function. Current Biology 14, 1135– 1147 (2004). 15242610
  4. [4]Stone MC, Normal spastin gene dosage is specifically required for axon regeneration. Cell reports 2, 1340– 1350 (2012). 23122959 PMC3513560
  5. [6]Stoppin-Mellet V, Gaillard J, Vantard M, Katanin’s severing activity favors bundling of cortical microtubules in plants. The Plant Journal 46, 1009– 1017 (2006). 16805733
  6. [7]Zhang Q, Fishel E, Bertroche T, Dixit R, Microtubule severing at crossover sites by katanin generates ordered cortical microtubule arrays in Arabidopsis. Current Biology 23, 2191– 2195 (2013). 24206847
  7. [8]Lindeboom JJ, A mechanism for reorientation of cortical microtubule arrays driven by microtubule severing. Science 342, 1245533 (2013). 24200811
  8. [9]Zhang D, Rogers GC, Buster DW, Sharp DJ, Three microtubule severing enzymes contribute to the “Pacman-flux” machinery that moves chromosomes. The Journal of cell biology 177, 231– 242 (2007). 17452528 PMC2064132
  9. [10]McNally K, Audhya A, Oegema K, McNally FJ, Katanin controls mitotic and meiotic spindle length. The Journal of cell biology 175, 881– 891 (2006). 17178907 PMC2064698
  10. [11]Loughlin R, Wilbur JD, McNally FJ, Nedelec FJ, Heald R, Katanin contributes to interspecies spindle length scaling in Xenopus. Cell 147, 1397– 1407 (2011). 22153081 PMC3240848
  11. [12]McNally K, Katanin maintains meiotic metaphase chromosome alignment and spindle structure in vivo and has multiple effects on microtubules in vitro. Molecular biology of the cell 25, 1037– 1049 (2014). 24501424 PMC3967969
  12. [13]Sharma N, Katanin regulates dynamics of microtubules and biogenesis of motile cilia. The Journal of cell biology 178, 1065– 1079 (2007). 17846175 PMC2064628
  13. [14]Hu WF, Katanin p80 regulates human cortical development by limiting centriole and cilia number. Neuron 84, 1240– 1257 (2014). 25521379 PMC4485387
  14. [15]Mishra-Gorur K, Mutations in KATNB1 cause complex cerebral malformations by disrupting asymmetrically dividing neural progenitors. Neuron 84, 1226– 1239 (2014). 25521378 PMC5024344
  15. [16]Connell JW, Lindon C, Luzio JP, Reid E, Spastin couples microtubule severing to membrane traffic in completion of cytokinesis and secretion. Traffic 10, 42– 56 (2009). 19000169 PMC2709849
  16. [17]Guizetti J, Cortical constriction during abscission involves helices of ESCRT-III- dependent filaments. Science 331, 1616– 1620 (2011). 21310966
  17. [18]Karabay A, Yu W, Solowska JM, Baird DH, Baas PW, Axonal growth is sensitive to the levels of katanin, a protein that severs microtubules. The Journal of neuroscience 24, 5778– 5788 (2004). 15215300 PMC6729225
  18. [19]Charafeddine RA, Fidgetin-Like 2: a microtubule-based regulator of wound healing. Journal of Investigative Dermatology 135, 2309– 2318 (2015). 25756798 PMC4537388
  19. [20]Yigit G, A syndrome of microcephaly, short stature, polysyndactyly, and dental anomalies caused by a homozygous KATNB1 mutation. American journal of medical geneticsPart A 170, 728– 733 (2016). 26640080
  20. [21]Roll-Mecak A, Vale RD, The Drosophila homologue of the hereditary spastic paraplegia protein, spastin, severs and disassembles microtubules. Current biology 15, 650– 655 (2005). 15823537
  21. [22]Jiang K, Microtubule minus-end regulation at spindle poles by an ASPM-katanin complex. Nature cell biology 19, 480 (2017). 28436967 PMC5458804
  22. [23]Wood JD, The microtubule-severing protein Spastin is essential for axon outgrowth in the zebrafish embryo. Human molecular genetics 15, 2763– 2771 (2006). 16893913
  23. [24]Burk DH, Ye Z-H, Alteration of oriented deposition of cellulose microfibrils by mutation of a katanin-like microtubule-severing protein. The Plant Cell 14, 2145– 2160 (2002). 12215512 PMC150762
  24. [25]Srayko M, O’Toole ET, Hyman AA, Muller-Reichert T, Katanin disrupts the microtubule lattice and increases polymer number in C. elegans meiosis. Current biology: CB 16, 1944– 1949 (2006). 17027492
  25. [26]Ribbeck K, Mitchison TJ, Meiotic spindle: sculpted by severing. Current biology 16, R923– R925 (2006). 17084690
  26. [27]Roll-Mecak A, Vale RD, Making more microtubules by severing: a common theme of noncentrosomal microtubule arrays? The Journal of cell biology 175, 849– 851 (2006). 17178905 PMC2064694
  27. [28]Walker R, Inoue S, Salmon E, Asymmetric behavior of severed microtubule ends after ultraviolet-microbeam irradiation of individual microtubules in vitro. The Journal of cell biology 108, 931– 937 (1989). 2921286 PMC2115382
  28. [29]Tran P, Walker R, Salmon E, A metastable intermediate state of microtubule dynamic instability that differs significantly between plus and minus ends. The Journal of cell biology 138, 105– 117 (1997). 9214385 PMC2139954
  29. [30]Mitchison T, Kirschner M, Dynamic instability of microtubule growth. Nature 312, 237– 242 (1984). 6504138
  30. [31]Carlier MF, Pantaloni D, Kinetic analysis of guanosine 5’-triphosphate hydrolysis associated with tubulin polymerization. Biochemistry 20, 1918– 1924 (1981). 7225365
  31. [32]Zhang D, Drosophila katanin is a microtubule depolymerase that regulates cortical- microtubule plus-end interactions and cell migration. Nature cell biology 13, 361– 369 (2011). 21378981 PMC3144748
  32. [33]Schaedel L, Microtubules self-repair in response to mechanical stress. Nature materials 14, 1156– 1163 (2015). 26343914 PMC4620915
  33. [34]Aumeier C, Self-repair promotes microtubule rescue. Nature cell biology 18, 1054– 1064 (2016). 27617929 PMC5045721
  34. [35]Bailey ME, Sackett DL, Ross JL, Katanin Severing and Binding Microtubules Are Inhibited by Tubulin Carboxy Tails. Biophysical journal 109, 2546– 2561 (2015). 26682813 PMC4699919
  35. [36]Hiller G, Weber K, Radioimmunoassay for tubulin: a quantitative comparison of the tubulin content of different established tissue culture cells and tissues. Cell 14, 795– 804 (1978). 688394
  36. [37]Itzhak DN, Tyanova S, Cox J, Borner GH, Global, quantitative and dynamic mapping of protein subcellular localization. Elife 5, e16950 (2016). PMC4959882 27278775
  37. [38]Vemu A, Structure and dynamics of single-isoform recombinant Neuronal Human Tubulin. Journal of Biological Chemistry, jbc. C116. 731133 (2016). PMC4933209 27129203
  38. [39]Carlier M-F, Guanosine-5′-triphosphate hydrolysis and tubulin polymerization. Molecular and cellular biochemistry 47, 97– 113 (1982). 6755216
  39. [40]Carlier MF, Pantaloni D, Assembly of microtubule protein: role of guanosine di-and triphosphate nucleotides. Biochemistry 21, 1215– 1224 (1982). 7074077
  40. [41]Carlier MF, Didry D, Pantaloni D, Microtubule elongation and guanosine 5′-triphosphate hydrolysis. Role of guanine nucleotides in microtubule dynamics. Biochemistry 26, 4428– 4437 (1987). 3663597
  41. [42]VanBuren V, Odde DJ, Cassimeris L, Estimates of lateral and longitudinal bond energies within the microtubule lattice. Proceedings of the National Academy of Sciences 99, 6035– 6040 (2002). PMC122897 11983898
  42. [43]Dimitrov A, Detection of GTP-tubulin conformation in vivo reveals a role for GTP remnants in microtubule rescues. Science 322, 1353– 1356 (2008). 18927356
  43. [44]Al-Bassam J, CLASP promotes microtubule rescue by recruiting tubulin dimers to the microtubule. Developmental cell 19, 245– 258 (2010). 20708587 PMC3156696
  44. [45]Ichihara K, Kitazawa H, Iguchi Y, Hotani H, Itoh TJ, Visualization of the stop of microtubule depolymerization that occurs at the high-density region of microtubule-associated protein 2 (MAP2). Journal of molecular biology 312, 107– 118 (2001). 11545589
  45. [46]Zanic M, Stear JH, Hyman AA, Howard J, EB1 recognizes the nucleotide state of tubulin in the microtubule lattice. PloS one 4, e7585 (2009). 19851462 PMC2761489
  46. [47]Maurer SP, Fourniol FJ, Bohner G, Moores CA, Surrey T, EBs recognize a nucleotide-dependent structural cap at growing microtubule ends. Cell 149, 371– 382 (2012). 22500803 PMC3368265
  47. [48]Spurck TP, UV microbeam irradiations of the mitotic spindle. II. Spindle fiber dynamics and force production. The Journal of cell biology 111, 1505– 1518 (1990). 2211823 PMC2116244
  48. [49]Brugués J, Nuzzo V, Mazur E, Needleman DJ, Nucleation and transport organize microtubules in metaphase spindles. Cell 149, 554– 564 (2012). 22541427
  49. [50]Nicklas RB, Lee GM, Rieder C, Rupp G, Mechanically cut mitotic spindles: clean cuts and stable microtubules. Journal of cell science 94, 415– 423 (1989). 2698889
  50. [51]Tirnauer JS, Salmon ED, Mitchison TJ, Microtubule plus-end dynamics in Xenopus egg extract spindles. Molecular biology of the cell 15, 1776– 1784 (2004). 14767058 PMC379274
  51. [52]Howard J, Hyman AA, Microtubule polymerases and depolymerases. Current opinion in cell biology 19, 31– 35 (2007). 17184986
  52. [53]Vale RD, Severing of stable microtubules by a mitotically activated protein in Xenopus egg extracts. Cell 64, 827– 839 (1991). 1671762
  53. [54]de Forges H, Localized mechanical stress promotes microtubule rescue. Current Biology 26, 3399– 3406 (2016). 27916523
  54. [55]Wang C, KTN80 confers precision to microtubule severing by specific targeting of katanin complexes in plant cells. The EMBO journal 36, 3435– 3447 (2017). 28978669 PMC5709764
  55. [56]Valenstein ML, Roll-Mecak A, Graded control of microtubule severing by tubulin glutamylation. Cell 164, 911– 921 (2016). 26875866 PMC6459029
  56. [57]Lacroix B, Tubulin polyglutamylation stimulates spastin-mediated microtubule severing. The Journal of cell biology 189, 945– 954 (2010). 20530212 PMC2886356
  57. [58]Nakata T, Niwa S, Okada Y, Perez F, Hirokawa N, Preferential binding of a kinesin-1 motor to GTP-tubulin-rich microtubules underlies polarized vesicle transport. The Journal of cell biology 194, 245– 255 (2011). 21768290 PMC3144414
  58. [59]Chan AY, Bailly M, Zebda N, Segall JE, Condeelis JS, Role of cofilin in epidermal growth factor-stimulated actin polymerization and lamellipod protrusion. The Journal of cell biology 148, 531– 542 (2000). 10662778 PMC2174812
  59. [60]DesMarais V, Ghosh M, Eddy R, Condeelis J, Cofilin takes the lead. J Cell Sci 118, 19– 26 (2005). 15615780
  60. [61]Ziolkowska NE, Roll-Mecak A, In vitro microtubule severing assays. Methods in molecular biology (Clifton, N.J.) 1046, 323– 334 (2013). 23868597
  61. [62]Zehr E, Katanin spiral and ring structures shed light on power stroke for microtubule severing. Nature structural & molecular biology 24, 717– 725 (2017). PMC7152510 28783150
  62. [63]Albee AJ, Wiese C, Xenopus TACC3/maskin is not required for microtubule stability but is required for anchoring microtubules at the centrosome. Molecular biology of the cell 19, 3347– 3356 (2008). 18508920 PMC2488304
  63. [64]Gell C, Purification of tubulin from porcine brain. Microtubule Dynamics: Methods and Protocols, 15– 28 (2011). 21773918
  64. [65]Edelstein AD, Advanced methods of microscope control using ^Manager software. Journal of biological methods 1, (2014). PMC4297649 25606571
  65. [66]Gibbons I, Fronk E, A latent adenosine triphosphatase form of dynein 1 from sea urchin sperm flagella. Journal of Biological Chemistry 254, 187– 196 (1979). 214440

Cited by

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Authors
Vemu, A., Szczesna, E., Zehr, E. A., Spector, J. O., Grigorieff, N., Deaconescu, A. M., & Roll-Mecak, A.
Affiliations
  • National Institutes of Health (US)
  • Cell Biology and Biophysics Unit, Porter Neuroscience Research Center, National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892, USA.
  • Howard Hughes Medical Institute (US)
  • Brown University (US)
Corresponding author
Vemu, Annapurna
ORCID
Venue
Science
Publisher
American Association for the Advancement of Science (AAAS)
Published
2018-08-24
Volume
361
Issue
6404
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
DOI
10.1126/science.aau1504
PMC
PMC6510489
OpenAlex
W2888209032
Cited by
210
References
1
Citations by year
2026: 16 · 2025: 19 · 2024: 20 · 2023: 26 · 2022: 33 · 2021: 26 · 2020: 33 · 2019: 30 · 2018: 7
FWCI
13.27
Type
journal article
Language
en
Open access
Locations
  • Science (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health
  • Howard Hughes Medical Institute
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Kidney Cyst Diseases
  • Health Sciences › Medicine › Oncology › Cancer Treatment and Pharmacology
Keywords
microtubule severing, spastin, katanin, microtubule rescue, microtubule dynamics, microtubule stability, microtubule plus ends
MeSH terms
Single Molecule Imaging, Spastin, Katanin, Animals, Drosophila melanogaster, Guanosine Triphosphate, Humans, Microscopy, Electron, Microscopy, Fluorescence, Microtubules, Tubulin, Caenorhabditis elegans

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