1932

Abstract

The microtubule (MT) cytoskeleton provides the architecture that governs intracellular organization and the regulated motion of macromolecules through the crowded cytoplasm. The key to establishing a functioning cytoskeletal architecture is regulating when and where new MTs are nucleated. Within the spindle, the vast majority of MTs are generated through a pathway known as branching MT nucleation, which exponentially amplifies MT number in a polar manner. Whereas other MT nucleation pathways generally require a complex organelle such as the centrosome or Golgi apparatus to localize nucleation factors, the branching site is based solely on a simple, preformed MT, making it an ideal system to study MT nucleation. In this review, we address recent developments in characterizing branching factors, the branching reaction, and its regulation, as well as branching MT nucleation in systems beyond the spindle and within human disease.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-cellbio-120420-114559
2022-10-06
2024-04-27
Loading full text...

Full text loading...

/deliver/fulltext/cellbio/38/1/annurev-cellbio-120420-114559.html?itemId=/content/journals/10.1146/annurev-cellbio-120420-114559&mimeType=html&fmt=ahah

Literature Cited

  1. Alfaro-Aco R, Thawani A, Petry S. 2017. Structural analysis of the role of TPX2 in branching microtubule nucleation. J. Cell Biol. 216:983–97
    [Google Scholar]
  2. Alfaro-Aco R, Thawani A, Petry S. 2020. Biochemical reconstitution of branching microtubule nucleation. eLife 9:e49797
    [Google Scholar]
  3. Alvarado-Kristensson M. 2018. γ-tubulin as a signal-transducing molecule and meshwork with therapeutic potential. Signal Transduct. Target. Ther. 3:24
    [Google Scholar]
  4. Boissan M, Schlattner U, Lacombe ML. 2018. The NDPK/NME superfamily: state of the art. Lab. Investig. 98:164–74
    [Google Scholar]
  5. Borek WE, Groocock LM, Samejima I, Zou J, de Lima Alves F et al. 2015. Mto2 multisite phosphorylation inactivates non-spindle microtubule nucleation complexes during mitosis. Nat. Commun. 6:7929
    [Google Scholar]
  6. Brilot AF, Lyon AS, Zelter A, Viswanath S, Maxwell A et al. 2021. CM1-driven assembly and activation of yeast gamma-tubulin small complex underlies microtubule nucleation. eLife 10:e65168
    [Google Scholar]
  7. Brouhard GJ, Stear JH, Noetzel TL, Al-Bassam J, Kinoshita K et al. 2008. XMAP215 is a processive microtubule polymerase. Cell 132:79–88
    [Google Scholar]
  8. Brugues J, Nuzzo V, Mazur E, Needleman DJ. 2012. Nucleation and transport organize microtubules in metaphase spindles. Cell 149:554–64
    [Google Scholar]
  9. Brunet S, Sardon T, Zimmerman T, Wittmann T, Pepperkok R et al. 2004. Characterization of the TPX2 domains involved in microtubule nucleation and spindle assembly in Xenopus egg extracts. Mol. Biol. Cell 15:5318–28
    [Google Scholar]
  10. Bucciarelli E, Pellacani C, Naim V, Palena A, Gatti M, Somma MP. 2009. Drosophila Dgt6 interacts with Ndc80, Msps/XMAP215, and γ-tubulin to promote kinetochore-driven MT formation. Curr. Biol. 19:1839–45
    [Google Scholar]
  11. Byrnes AE, Slep KC. 2017. TOG-tubulin binding specificity promotes microtubule dynamics and mitotic spindle formation. J. Cell Biol. 216:1641–57
    [Google Scholar]
  12. Carazo-Salas RE, Guarguaglini G, Gruss OJ, Segref A, Karsenti E, Mattaj IW. 1999. Generation of GTP-bound Ran by RCC1 is required for chromatin-induced mitotic spindle formation. Nature 400:178–81
    [Google Scholar]
  13. Cavazza T, Vernos I. 2015. The RanGTP pathway: from nucleo-cytoplasmic transport to spindle assembly and beyond. Front. Cell Dev. Biol. 3:82
    [Google Scholar]
  14. Chan J, Sambade A, Calder G, Lloyd C. 2009. Arabidopsis cortical microtubules are initiated along, as well as branching from, existing microtubules. Plant Cell 21:2298–306
    [Google Scholar]
  15. Chen JWC, Chen ZA, Rogala KB, Metz J, Deane CM et al. 2017. Cross-linking mass spectrometry identifies new interfaces of Augmin required to localise the γ-tubulin ring complex to the mitotic spindle. Biol. Open 6:654–63
    [Google Scholar]
  16. Chen W-S, Chen Y-J, Huang Y-A, Hsieh B-Y, Chiu H-C et al. 2017. Ran-dependent TPX2 activation promotes acentrosomal microtubule nucleation in neurons. Sci. Rep. 7:42297
    [Google Scholar]
  17. Chinen T, Liu P, Shioda S, Pagel J, Cerikan B et al. 2015. The γ-tubulin-specific inhibitor gatastatin reveals temporal requirements of microtubule nucleation during the cell cycle. Nat. Commun. 6:8722
    [Google Scholar]
  18. Choi Y-K, Liu P, Sze SK, Dai C, Qi RZ. 2010. CDK5RAP2 stimulates microtubule nucleation by the γ-tubulin ring complex. J. Cell Biol. 191:1089–95
    [Google Scholar]
  19. Clausen T, Ribbeck K. 2007. Self-organization of anastral spindles by synergy of dynamic instability, autocatalytic microtubule production, and a spatial signaling gradient. PLOS ONE 2:e244
    [Google Scholar]
  20. Consolati T, Locke J, Roostalu J, Chen ZA, Gannon J et al. 2020. Microtubule nucleation properties of single human γTuRCs explained by their cryo-EM structure. Dev. Cell 53:603–17.e8
    [Google Scholar]
  21. Cota RR, Teixido-Travesa N, Ezquerra A, Eibes S, Lacasa C et al. 2017. MZT1 regulates microtubule nucleation by linking γTuRC assembly to adapter-mediated targeting and activation. J. Cell Sci. 130:406–19
    [Google Scholar]
  22. Courthéoux T, Reboutier D, Vazeille T, Cremet J-Y, Benaud C et al. 2019. Microtubule nucleation during central spindle assembly requires NEDD1 phosphorylation on serine 405 by Aurora A. J. Cell Sci. 132:jcs231118
    [Google Scholar]
  23. Cunha-Ferreira I, Chazeau A, Buijs RR, Stucchi R, Will L et al. 2018. The HAUS complex is a key regulator of non-centrosomal microtubule organization during neuronal development. Cell Rep. 24:791–800
    [Google Scholar]
  24. David AF, Roudot P, Legant WR, Betzig E, Danuser G, Gerlich DW. 2019. Augmin accumulation on long-lived microtubules drives amplification and kinetochore-directed growth. J. Cell Biol. 218:2150–68
    [Google Scholar]
  25. de Cárcer G. 2019. The mitotic cancer target Polo-like kinase 1: oncogene or tumor suppressor?. Genes 10:208
    [Google Scholar]
  26. Decker F, Oriola D, Dalton B, Brugués J. 2018. Autocatalytic microtubule nucleation determines the size and mass of Xenopus laevis egg extract spindles. eLife 7:e31149
    [Google Scholar]
  27. Ding Y, Herman JA, Toledo CM, Lang JM, Corrin P et al. 2017. ZNF131 suppresses centrosome fragmentation in glioblastoma stem-like cells through regulation of HAUS5. Oncotarget 8:48545–62
    [Google Scholar]
  28. Dráber P, Dráberová E. 2021. Dysregulation of microtubule nucleating proteins in cancer cells. Cancers 13:5638
    [Google Scholar]
  29. Dráberová E, D'Agostino L, Caracciolo V, Sládková V, Sulimenko T et al. 2015. Overexpression and nucleolar localization of γ-tubulin small complex proteins GCP2 and GCP3 in glioblastoma. J. Neuropathol. Exp. Neurol. 74:723–42
    [Google Scholar]
  30. Ebisu H, Shintani K, Chinen T, Nagumo Y, Shioda S et al. 2020. Dual inhibition of γ-tubulin and Plk1 induces mitotic cell death. Front. Pharmacol. 11:620185
    [Google Scholar]
  31. Eckerdt F, Eyers PA, Lewellyn AL, Prigent C, Maller JL. 2008. Spindle pole regulation by a discrete Eg5-interacting domain in TPX2. Curr. Biol. 18:519–25
    [Google Scholar]
  32. Eckerdt F, Pascreau G, Phistry M, Lewellyn AL, DePaoli-Roach AA, Maller JL. 2009. Phosphorylation of TPX2 by Plx1 enhances activation of Aurora A. Cell Cycle 8:2413–19
    [Google Scholar]
  33. Edzuka T, Yamada L, Kanamaru K, Sawada H, Goshima G. 2014. Identification of the augmin complex in the filamentous fungus Aspergillus nidulans. PLOS ONE 9:e101471
    [Google Scholar]
  34. Eibes S, Gallisa-Sune N, Rosas-Salvans M, Martinez-Delgado P, Vernos I, Roig J. 2018. Nek9 phosphorylation defines a new role for TPX2 in Eg5-dependent centrosome separation before nuclear envelope breakdown. Curr. Biol. 28:121–29.e4
    [Google Scholar]
  35. Findeisen P, Muhlhausen S, Dempewolf S, Hertzog J, Zietlow A et al. 2014. Six subgroups and extensive recent duplications characterize the evolution of the eukaryotic tubulin protein family. Genome Biol. Evol. 6:2274–88
    [Google Scholar]
  36. Flor-Parra I, Iglesias-Romero AB, Chang F 2018. The XMAP215 ortholog Alp14 promotes microtubule nucleation in fission yeast. Curr. Biol. 28:1681–91.e4
    [Google Scholar]
  37. Forbes DJ, Travesa A, Nord MS, Bernis C. 2015. Nuclear transport factors: global regulation of mitosis. Curr. Opin. Cell Biol. 35:78–90
    [Google Scholar]
  38. Fox JC, Howard AE, Currie JD, Rogers SL, Slep KC. 2014. The XMAP215 family drives microtubule polymerization using a structurally diverse TOG array. Mol. Biol. Cell 25:2375–92
    [Google Scholar]
  39. Fry AM, O'Regan L, Montgomery J, Adib R, Bayliss R. 2016. EML proteins in microtubule regulation and human disease. Biochem. Soc. Trans. 44:1281–88
    [Google Scholar]
  40. Fu J, Bian M, Xin G, Deng Z, Luo J et al. 2015. TPX2 phosphorylation maintains metaphase spindle length by regulating microtubule flux. J. Cell Biol. 210:373–83
    [Google Scholar]
  41. Gai Y, Cook B, Setru S, Stone HA, Petry S. 2021. Confinement size determines the architecture of Ran-induced microtubule networks. Soft Matter 17:5921–31
    [Google Scholar]
  42. Gard DL, Becker BE, Romney SJ. 2004. MAPping the eukaryotic tree of life: structure, function, and evolution of the MAP215/Dis1 family of microtubule-associated proteins. Int. Rev. Cytol. 239:179–272
    [Google Scholar]
  43. Gard DL, Kirschner MW. 1987. A microtubule-associated protein from Xenopus eggs that specifically promotes assembly at the plus-end. J. Cell Biol. 105:2203–15
    [Google Scholar]
  44. Garrido G, Vernos I. 2016. Non-centrosomal TPX2-dependent regulation of the Aurora A kinase: functional implications for healthy and pathological cell division. Front. Oncol. 6:88
    [Google Scholar]
  45. Giesecke A, Stewart M. 2010. Novel binding of the mitotic regulator TPX2 (target protein for Xenopus kinesin-like protein 2) to importin-α. J. Biol. Chem. 285:17628–35
    [Google Scholar]
  46. Gomez-Ferreria MA, Bashkurov M, Helbig AO, Larsen B, Pawson T et al. 2012. Novel NEDD1 phosphorylation sites regulate γ-tubulin binding and mitotic spindle assembly. J. Cell Sci. 125:3745–51
    [Google Scholar]
  47. Goshima G. 2011. Identification of a TPX2-like microtubule-associated protein in Drosophila. PLOS ONE 6:e28120
    [Google Scholar]
  48. Goshima G, Mayer M, Zhang N, Stuurman N, Vale RD. 2008. Augmin: a protein complex required for centrosome-independent microtubule generation within the spindle. J. Cell Biol. 181:421–29
    [Google Scholar]
  49. Goshima G, Wollman R, Goodwin SS, Zhang N, Scholey JM et al. 2007. Genes required for mitotic spindle assembly in Drosophila S2 cells. Science 316:417–21
    [Google Scholar]
  50. Groen AC, Cameron LA, Coughlin M, Miyamoto DT, Mitchison TJ, Ohi R. 2004. XRHAMM functions in ran-dependent microtubule nucleation and pole formation during anastral spindle assembly. Curr. Biol. 14:1801–11
    [Google Scholar]
  51. Gruss OJ, Carazo-Salas RE, Schatz CA, Guarguaglini G, Kast J et al. 2001. Ran induces spindle assembly by reversing the inhibitory effect of importin α on TPX2 activity. Cell 104:83–93
    [Google Scholar]
  52. Gruss OJ, Vernos I. 2004. The mechanism of spindle assembly: functions of Ran and its target TPX2. J. Cell Biol. 166:949–55
    [Google Scholar]
  53. Guillet V, Knibiehler M, Gregory-Pauron L, Remy MH, Chemin C et al. 2011. Crystal structure of γ-tubulin complex protein GCP4 provides insight into microtubule nucleation. Nat. Struct. Mol. Biol. 18:915–19
    [Google Scholar]
  54. Gunawardane RN, Martin OC, Zheng Y. 2003. Characterization of a new γTuRC subunit with WD repeats. Mol. Biol. Cell 14:1017–26
    [Google Scholar]
  55. Gunzelmann J, Rüthnick D, Lin T-C, Zhang W, Neuner A et al. 2018. The microtubule polymerase Stu2 promotes oligomerization of the γ-TuSC for cytoplasmic microtubule nucleation. eLife 7:e39932
    [Google Scholar]
  56. Haren L, Remy MH, Bazin I, Callebaut I, Wright M, Merdes A. 2006. NEDD1-dependent recruitment of the γ-tubulin ring complex to the centrosome is necessary for centriole duplication and spindle assembly. J. Cell Biol. 172:505–15
    [Google Scholar]
  57. Ho C-MK, Hotta T, Kong Z, Zeng CJT, Sun J et al. 2011. Augmin plays a critical role in organizing the spindle and phragmoplast microtubule arrays in Arabidopsis. Plant Cell 23:2606–18
    [Google Scholar]
  58. Howard AE, Fox JC, Slep KC. 2015. Drosophila melanogaster mini spindles TOG3 utilizes unique structural elements to promote domain stability and maintain a TOG1- and TOG2-like tubulin-binding surface. J. Biol. Chem. 290:10149–62
    [Google Scholar]
  59. Hsia K-C, Wilson-Kubalek EM, Dottore A, Hao Q, Tsai K-L et al. 2014. Reconstitution of the augmin complex provides insights into its architecture and function. Nat. Cell Biol. 16:852–63
    [Google Scholar]
  60. Huang T-L, Wang H-J, Chang Y-C, Wang S-W, Hsia K-C. 2020. Promiscuous binding of microprotein Mozart1 to γ-tubulin complex mediates specific subcellular targeting to control microtubule array formation. Cell Rep. 31:107836
    [Google Scholar]
  61. Hughes JR, Meireles AM, Fisher KH, Garcia A, Antrobus PR et al. 2008. A microtubule interactome: complexes with roles in cell cycle and mitosis. PLOS Biol. 6:e98
    [Google Scholar]
  62. Hutchins JR, Toyoda Y, Hegemann B, Poser I, Heriche JK et al. 2010. Systematic analysis of human protein complexes identifies chromosome segregation proteins. Science 328:593–99
    [Google Scholar]
  63. Janson ME, Setty TG, Paoletti A, Tran PT. 2005. Efficient formation of bipolar microtubule bundles requires microtubule-bound γ-tubulin complexes. J. Cell Biol. 169:297–308
    [Google Scholar]
  64. Johmura Y, Soung N-K, Park J-E, Yu LR, Zhou M et al. 2011. Regulation of microtubule-based microtubule nucleation by mammalian polo-like kinase 1. PNAS 108:11446–51
    [Google Scholar]
  65. Kamasaki T, O'Toole E, Kita S, Osumi M, Usukura J et al. 2013. Augmin-dependent microtubule nucleation at microtubule walls in the spindle. J. Cell Biol. 202:25–33
    [Google Scholar]
  66. King BR, Moritz M, Kim H, Agard DA, Asbury CL, Davis TN. 2020. XMAP215 and γ-tubulin additively promote microtubule nucleation in purified solutions. Mol. Biol. Cell 31:2187–94
    [Google Scholar]
  67. King MR, Petry S. 2020. Phase separation of TPX2 enhances and spatially coordinates microtubule nucleation. Nat. Commun. 11:270
    [Google Scholar]
  68. Kirik A, Ehrhardt DW, Kirik V. 2012. TONNEAU2/FASS regulates the geometry of microtubule nucleation and cortical array organization in interphase Arabidopsis cells. Plant Cell 24:1158–70
    [Google Scholar]
  69. Knop M, Pereira G, Geissler S, Grein K, Schiebel E. 1997. The spindle pole body component Spc97p interacts with the γ-tubulin of Saccharomyces cerevisiae and functions in microtubule organization and spindle pole body duplication. EMBO J. 16:1550–64
    [Google Scholar]
  70. Kollman JM, Polka JK, Zelter A, Davis TN, Agard DA. 2010. Microtubule nucleating γ-TuSC assembles structures with 13-fold microtubule-like symmetry. Nature 466:879–82
    [Google Scholar]
  71. Kong Z, Hotta T, Lee YR, Horio T, Liu B. 2010. The γ-tubulin complex protein GCP4 is required for organizing functional microtubule arrays in Arabidopsis thaliana. Plant Cell 22:191–204
    [Google Scholar]
  72. Lawo S, Bashkurov M, Mullin M, Ferreria MG, Kittler R et al. 2009. HAUS, the 8-subunit human Augmin complex, regulates centrosome and spindle integrity. Curr. Biol. 19:816–26
    [Google Scholar]
  73. Lee YJ, Hiwatashi Y, Hotta T, Xie T, Doonan JH, Liu B. 2017. The mitotic function of Augmin is dependent on its microtubule-associated protein subunit EDE1 in Arabidopsis thaliana. Curr. Biol. 27:3891–97.e4
    [Google Scholar]
  74. Lin T-C, Neuner A, Schlosser YT, Scharf AND, Weber L, Schiebel E. 2014. Cell-cycle dependent phosphorylation of yeast pericentrin regulates γ-TuSC-mediated microtubule nucleation. eLife 3:e02208
    [Google Scholar]
  75. Liu P, Choi YK, Qi RZ. 2014. NME7 is a functional component of the γ-tubulin ring complex. Mol. Biol. Cell 25:2017–25
    [Google Scholar]
  76. Liu P, Zupa E, Neuner A, Bohler A, Loerke J et al. 2020. Insights into the assembly and activation of the microtubule nucleator γ-TuRC. Nature 578:467–71
    [Google Scholar]
  77. Loughlin R, Heald R, Nedelec F. 2010. A computational model predicts Xenopus meiotic spindle organization. J. Cell Biol. 191:1239–49
    [Google Scholar]
  78. Luders J, Patel UK, Stearns T. 2006. GCP-WD is a γ-tubulin targeting factor required for centrosomal and chromatin-mediated microtubule nucleation. Nat. Cell Biol. 8:137–47
    [Google Scholar]
  79. Luo J, Yang B, Xin G, Sun M, Zhang B et al. 2019. The microtubule-associated protein EML3 regulates mitotic spindle assembly by recruiting the Augmin complex to spindle microtubules. J. Biol. Chem. 294:5643–56
    [Google Scholar]
  80. Lynch EM, Groocock LM, Borek WE, Sawin KE. 2014. Activation of the γ-tubulin complex by the Mto1/2 complex. Curr. Biol. 24:896–903
    [Google Scholar]
  81. Ma N, Titus J, Gable A, Ross JL, Wadsworth P. 2011. TPX2 regulates the localization and activity of Eg5 in the mammalian mitotic spindle. J. Cell Biol. 195:87–98
    [Google Scholar]
  82. Ma N, Tulu US, Ferenz NP, Fagerstrom C, Wilde A, Wadsworth P. 2010. Poleward transport of TPX2 in the mammalian mitotic spindle requires dynein, Eg5, and microtubule flux. Mol. Biol. Cell 21:979–88
    [Google Scholar]
  83. Mahoney NM, Goshima G, Douglass AD, Vale RD. 2006. Making microtubules and mitotic spindles in cells without functional centrosomes. Curr. Biol. 16:564–69
    [Google Scholar]
  84. Mann BJ, Balchand SK, Wadsworth P. 2017. Regulation of Kif15 localization and motility by the C-terminus of TPX2 and microtubule dynamics. Mol. Biol. Cell 28:65–75
    [Google Scholar]
  85. Meireles AM, Fisher KH, Colombie N, Wakefield JG, Ohkura H. 2009. Wac: a new Augmin subunit required for chromosome alignment but not for acentrosomal microtubule assembly in female meiosis. J. Cell Biol. 184:777–84
    [Google Scholar]
  86. Murata T, Sonobe S, Baskin TI, Hyodo S, Hasezawa S et al. 2005. Microtubule-dependent microtubule nucleation based on recruitment of γ-tubulin in higher plants. Nat. Cell Biol. 7:961–68
    [Google Scholar]
  87. Nakamura M, Hashimoto T. 2009. A mutation in the Arabidopsis γ-tubulin-containing complex causes helical growth and abnormal microtubule branching. J. Cell Sci. 122:2208–17
    [Google Scholar]
  88. Neumayer G, Belzil C, Gruss OJ, Nguyen MD. 2014. TPX2: of spindle assembly, DNA damage response, and cancer. Cell. Mol. Life Sci. 71:3027–47
    [Google Scholar]
  89. Nithianantham S, Cook BD, Beans M, Guo F, Chang F, Al-Bassam J. 2018. Structural basis of tubulin recruitment and assembly by microtubule polymerases with tumor overexpressed gene (TOG) domain arrays. eLife 7:e38922
    [Google Scholar]
  90. Oakley BR, Oakley CE, Yoon Y, Jung MK. 1990. γ-Tubulin is a component of the spindle pole body that is essential for microtubule function in Aspergillus nidulans. Cell 61:1289–301
    [Google Scholar]
  91. Oakley CE, Oakley BR. 1989. Identification of γ-tubulin, a new member of the tubulin superfamily encoded by mipA gene of Aspergillus nidulans. Nature 338:662–64
    [Google Scholar]
  92. Oh D, Yu CH, Needleman DJ. 2016. Spatial organization of the Ran pathway by microtubules in mitosis. PNAS 113:8729–34
    [Google Scholar]
  93. Ohba T, Nakamura M, Nishitani H, Nishimoto T. 1999. Self-organization of microtubule asters induced in Xenopus egg extracts by GTP-bound Ran. Science 284:1356–58
    [Google Scholar]
  94. Olsen JV, Vermeulen M, Santamaria A, Kumar C, Miller ML et al. 2010. Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci. Signal. 3:ra3
    [Google Scholar]
  95. Petry S, Groen AC, Ishihara K, Mitchison TJ, Vale RD. 2013. Branching microtubule nucleation in Xenopus egg extracts mediated by augmin and TPX2. Cell 152:768–77
    [Google Scholar]
  96. Petry S, Pugieux C, Nedelec FJ, Vale RD. 2011. Augmin promotes meiotic spindle formation and bipolarity in Xenopus egg extracts. PNAS 108:14473–78
    [Google Scholar]
  97. Peuchen EH, Cox OF, Sun L, Hebert AS, Coon JJ et al. 2017. Phosphorylation dynamics dominate the regulated proteome during early Xenopus development. Sci. Rep. 7:15647
    [Google Scholar]
  98. Pignocchi C, Minns GE, Nesi N, Koumproglou R, Kitsios G et al. 2009. ENDOSPERM DEFECTIVE1 is a novel microtubule-associated protein essential for seed development in Arabidopsis. Plant Cell 21:90–105
    [Google Scholar]
  99. Pinyol R, Scrofani J, Vernos I. 2013. The role of NEDD1 phosphorylation by Aurora A in chromosomal microtubule nucleation and spindle function. Curr. Biol. 23:143–49
    [Google Scholar]
  100. Reid TA, Schuster BM, Mann BJ, Balchand SK, Plooster M et al. 2016. Suppression of microtubule assembly kinetics by the mitotic protein TPX2. J. Cell Sci. 129:1319–28
    [Google Scholar]
  101. Roostalu J, Cade NI, Surrey T. 2015. Complementary activities of TPX2 and chTOG constitute an efficient importin-regulated microtubule nucleation module. Nat. Cell Biol. 17:1422–34
    [Google Scholar]
  102. Roostalu J, Surrey T. 2017. Microtubule nucleation: beyond the template. Nat. Rev. Mol. Cell Biol. 18:702–10
    [Google Scholar]
  103. Rostkova E, Burgess SG, Bayliss R, Pfuhl M. 2018. Solution NMR assignment of the C-terminal domain of human chTOG. Biomol. NMR Assign. 12:221–24
    [Google Scholar]
  104. Safari MS, King MR, Brangwynne CP, Petry S. 2021. Interaction of spindle assembly factor TPX2 with importins-α/β inhibits protein phase separation. J. Biol. Chem. 297:100998
    [Google Scholar]
  105. Samejima I, Miller VJ, Groocock LM, Sawin KE. 2008. Two distinct regions of Mto1 are required for normal microtubule nucleation and efficient association with the γ-tubulin complex in vivo. J. Cell Sci. 121:3971–80
    [Google Scholar]
  106. Sanchez-Huertas C, Freixo F, Viais R, Lacasa C, Soriano E, Luders J. 2016. Non-centrosomal nucleation mediated by augmin organizes microtubules in post-mitotic neurons and controls axonal microtubule polarity. Nat. Commun. 7:12187
    [Google Scholar]
  107. Sanchez-Huertas C, Luders J. 2015. The augmin connection in the geometry of microtubule networks. Curr. Biol. 25:R294–99
    [Google Scholar]
  108. Schatz CA, Santarella R, Hoenger A, Karsenti E, Mattaj IW et al. 2003. Importin α-regulated nucleation of microtubules by TPX2. EMBO J. 22:2060–70
    [Google Scholar]
  109. Schvartzman JM, Sotillo R, Benezra R. 2010. Mitotic chromosomal instability and cancer: mouse modelling of the human disease. Nat. Rev. Cancer 10:102–15
    [Google Scholar]
  110. Schweizer N, Haren L, Dutto I, Viais R, Lacasa C et al. 2021. Sub-centrosomal mapping identifies augmin-γTuRC as part of a centriole-stabilizing scaffold. Nat. Commun. 12:6042
    [Google Scholar]
  111. Scrofani J, Sardon T, Meunier S, Vernos I. 2015. Microtubule nucleation in mitosis by a RanGTP-dependent protein complex. Curr. Biol. 25:131–40
    [Google Scholar]
  112. Setru SU, Gouveia B, Alfaro-Aco R, Shaevitz JW, Stone HA, Petry S. 2021. A hydrodynamic instability drives protein droplet formation on microtubules to nucleate branches. Nat. Phys. 17:493–98
    [Google Scholar]
  113. Shah SP, Morin RD, Khattra J, Prentice L, Pugh T et al. 2009. Mutational evolution in a lobular breast tumour profiled at single nucleotide resolution. Nature 461:7265809–13
    [Google Scholar]
  114. Song JG, King MR, Zhang R, Kadzik RS, Thawani A, Petry S. 2018. Mechanism of how augmin directly targets the γ-tubulin ring complex to microtubules. J. Cell Biol. 217:2417–28
    [Google Scholar]
  115. Steblyanko Y, Rajendraprasad G, Osswald M, Eibes S, Jacome A et al. 2020. Microtubule poleward flux in human cells is driven by the coordinated action of four kinesins. EMBO J. 39:e105432
    [Google Scholar]
  116. Tanenbaum ME, Macurek L, Janssen A, Geers EF, Alvarez-Fernandez M, Medema RH. 2009. Kif15 cooperates with Eg5 to promote bipolar spindle assembly. Curr. Biol. 19:1703–11
    [Google Scholar]
  117. Tariq A, Green L, Jeynes JCG, Soeller C, Wakefield JG. 2020. In vitro reconstitution of branching microtubule nucleation. eLife 9:e49769
    [Google Scholar]
  118. Thawani A, Kadzik RS, Petry S. 2018. XMAP215 is a microtubule nucleation factor that functions synergistically with the γ-tubulin ring complex. Nat. Cell Biol. 20:575–85
    [Google Scholar]
  119. Thawani A, Rale MJ, Coudray N, Bhabha G, Stone HA et al. 2020. The transition state and regulation of γ-TuRC-mediated microtubule nucleation revealed by single molecule microscopy. eLife 9:e54253
    [Google Scholar]
  120. Thawani A, Stone HA, Shaevitz JW, Petry S. 2019. Spatiotemporal organization of branched microtubule networks. eLife 8:e43890
    [Google Scholar]
  121. Tian J, Kong Z. 2019. The role of the augmin complex in establishing microtubule arrays. J. Exp. Bot. 70:3035–41
    [Google Scholar]
  122. Tiwary AK, Zheng Y. 2019. Protein phase separation in mitosis. Curr. Opin. Cell Biol. 60:92–98
    [Google Scholar]
  123. Tovey CA, Conduit PT. 2018. Microtubule nucleation by γ-tubulin complexes and beyond. Essays Biochem. 62:765–80
    [Google Scholar]
  124. Traversi G, Staid DS, Fiore M, Percario Z, Trisciuoglio D et al. 2019. A novel resveratrol derivative induces mitotic arrest, centrosome fragmentation and cancer cell death by inhibiting γ-tubulin. Cell Div 14:3
    [Google Scholar]
  125. Tsai CY, Ngo B, Tapadia A, Hsu P-H, Wu G, Lee W-H. 2011. Aurora-A phosphorylates Augmin complex component Hice1 protein at an N-terminal serine/threonine cluster to modulate its microtubule binding activity during spindle assembly. J. Biol. Chem. 286:30097–106
    [Google Scholar]
  126. Uehara R, Goshima G. 2010. Functional central spindle assembly requires de novo microtubule generation in the interchromosomal region during anaphase. J. Cell Biol. 191:259–67
    [Google Scholar]
  127. Uehara R, Nozawa RS, Tomioka A, Petry S, Vale RD et al. 2009. The augmin complex plays a critical role in spindle microtubule generation for mitotic progression and cytokinesis in human cells. PNAS 106:6998–7003
    [Google Scholar]
  128. van Gijn SE, Wierenga E, van den Tempel N, Kok YP, Heijink AM et al. 2019. TPX2/Aurora kinase A signaling as a potential therapeutic target in genomically unstable cancer cells. Oncogene 38:852–67
    [Google Scholar]
  129. Verma V, Maresca TJ. 2019. Direct observation of branching MT nucleation in living animal cells. J. Cell Biol. 218:2829–40
    [Google Scholar]
  130. Viais R, Fariña-Mosquera M, Villamor-Payà M, Watanabe S, Palenzuela L et al. 2021. Augmin deficiency in neural stem cells causes p53-dependent apoptosis and aborts brain development. eLife 10:e67989
    [Google Scholar]
  131. Vos JW, Pieuchot L, Evrard JL, Janski N, Bergdoll M et al. 2008. The plant TPX2 protein regulates prospindle assembly before nuclear envelope breakdown. Plant Cell 20:2783–97
    [Google Scholar]
  132. Wainman A, Buster DW, Duncan T, Metz J, Ma A et al. 2009. A new Augmin subunit, Msd1, demonstrates the importance of mitotic spindle-templated microtubule nucleation in the absence of functioning centrosomes. Genes Dev. 23:1876–81
    [Google Scholar]
  133. Watanabe S, Shioi G, Furuta Y, Goshima G. 2016. Intra-spindle microtubule assembly regulates clustering of microtubule-organizing centers during early mouse development. Cell Rep. 15:54–60
    [Google Scholar]
  134. Widlund PO, Stear JH, Pozniakovsky A, Zanic M, Reber S et al. 2011. XMAP215 polymerase activity is built by combining multiple tubulin-binding TOG domains and a basic lattice-binding region. PNAS 108:2741–46
    [Google Scholar]
  135. Wieczorek M, Bechstedt S, Chaaban S, Brouhard GJ. 2015. Microtubule-associated proteins control the kinetics of microtubule nucleation. Nat. Cell Biol. 17:907–16
    [Google Scholar]
  136. Wieczorek M, Huang T-L, Urnavicius L, Hsia K-C, Kapoor TM. 2020a. MZT proteins form multi-faceted structural modules in the γ-tubulin ring complex. Cell Rep. 31:107791
    [Google Scholar]
  137. Wieczorek M, Urnavicius L, Ti SC, Molloy KR, Chait BT, Kapoor TM. 2020b. Asymmetric molecular architecture of the human γ-tubulin ring complex. Cell 180:165–75.e16
    [Google Scholar]
  138. Wittmann T, Boleti H, Antony C, Karsenti E, Vernos I. 1998. Localization of the kinesin-like protein Xklp2 to spindle poles requires a leucine zipper, a microtubule-associated protein, and dynein. J. Cell Biol. 143:673–85
    [Google Scholar]
  139. Wittmann T, Wilm M, Karsenti E, Vernos I. 2000. TPX2, a novel Xenopus MAP involved in spindle pole organization. J. Cell Biol. 149:1405–18
    [Google Scholar]
  140. Wu G, Lin Y-T, Wei R, Chen Y, Shan Z, Lee W-H. 2008. Hice1, a novel microtubule-associated protein required for maintenance of spindle integrity and chromosomal stability in human cells. Mol. Cell. Biol. 28:3652–62
    [Google Scholar]
  141. Wurtz M, Zupa E, Atorino ES, Neuner A, Bohler A et al. 2022. Modular assembly of the principal microtubule nucleator γ-TuRC. Nat. Commun. 13:473
    [Google Scholar]
  142. Yang G, Cameron LA, Maddox PS, Salmon ED, Danuser G. 2008. Regional variation of microtubule flux reveals microtubule organization in the metaphase meiotic spindle. J. Cell Biol. 182:631–39
    [Google Scholar]
  143. Yi P, Goshima G. 2018. Microtubule nucleation and organization without centrosomes. Curr. Opin. Plant Biol. 46:1–7
    [Google Scholar]
  144. Zahreddine H, Borden KL. 2013. Mechanisms and insights into drug resistance in cancer. Front. Pharmacol. 4:28
    [Google Scholar]
  145. Zasadil LM, Andersen KA, Yeum D, Rocque GB, Wilke LG et al. 2014. Cytotoxicity of paclitaxel in breast cancer is due to chromosome missegregation of multipolar spindles. Sci. Transl. Med. 6:3007965
    [Google Scholar]
  146. Zhang R, Roostalu J, Surrey T, Nogales E. 2017. Structural insight into TPX2-stimulated microtubule assembly. eLife 6:e30959
    [Google Scholar]
  147. Zhang X, Chen Q, Feng J, Hou J, Yang F et al. 2009. Sequential phosphorylation of Nedd1 by Cdk1 and Plk1 is required for targeting of the γTuRC to the centrosome. J. Cell Sci. 122:2240–51
    [Google Scholar]
  148. Zhang X, Zhuang R, Ye Q, Zhuo J, Chen K et al. 2019. High expression of human AugminComplex Submit 3 indicates poor prognosis and associates with tumor progression in hepatocellular carcinoma. J. Cancer 10:1434–43
    [Google Scholar]
  149. Zheng Y, Wong ML, Alberts B, Mitchison T. 1995. Nucleation of microtubule assembly by a γ-tubulin-containing ring complex. Nature 378:578–83
    [Google Scholar]
  150. Zhu H, Coppinger JA, Jang CY, Yates JR 3rd, Fang G. 2008. FAM29A promotes microtubule amplification via recruitment of the NEDD1-γ-tubulin complex to the mitotic spindle. J. Cell Biol. 183:835–48
    [Google Scholar]
  151. Zou J, Huang R-Y, Jiang F-N, Chen D-X, Wang C et al. 2018. Overexpression of TPX2 is associated with progression and prognosis of prostate cancer. Oncol. Lett. 16:2823–32
    [Google Scholar]
  152. Zupa E, Zheng A, Neuner A, Wurtz M, Liu P et al. 2020. The cryo-EM structure of a γ-TuSC elucidates architecture and regulation of minimal microtubule nucleation systems. Nat. Commun. 11:5705
    [Google Scholar]
/content/journals/10.1146/annurev-cellbio-120420-114559
Loading
/content/journals/10.1146/annurev-cellbio-120420-114559
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error