CoChat
Sign Up
Cited by 154Microtubule and mitosis dynamicsCancer Treatment and PharmacologySynthesis and biological activity

Kinesin-13s in mitosis: Key players in the spatial and temporal organization of spindle microtubules

Open access
Ems-McClung, Stephanie C., Walczak, Claire E.·2010·Seminars in Cell & Developmental Biology
DOI 10.1016/j.semcdb.2010.01.016PMC PMC2844478
Open this paper in CoChat — free account

Abstract

Dynamic microtubules are essential for the process of mitosis. Thus, elucidating when, where, and how microtubule dynamics are regulated is key to understanding this process. One important class of proteins that directly regulates microtubule dynamics is the Kinesin-13 family. Kinesin-13 proteins induce depolymerization uniquely from both ends of the microtubule. This activity coincides with their cellular localization and with their ability to regulate microtubule dynamics to control spindle assembly and kinetochore-microtubule attachments. In this review, we highlight recent findings that dissect the important actions of Kinesin-13 family members and summarize important studies on the regulation of their activity by phosphorylation and by protein-protein interactions.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1016/j.semcdb.2010.01.016

Cites

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Overexpression of Kif2a had no effect on CIN despite exhibiting microtubule-depolymerizing activity on interphase microtubules.

    “we overexpressed Kif2a, a third member of the kinesin-13 proteins that lacks kinetochore and centromere localization domains13, and observed no effect on CIN despite exhibiting microtubule-depolymerizing activity on interphase microtubules”

    From Chromosomal instability drives metastasis through a cytosolic DNA response (2018) · cites this paper as [13]

    The citation is attached to the description of Kif2A, not to the citing authors’ own overexpression and CIN results. Section 3.1 identifies Kif2A as a kinesin-13 found mainly at spindle poles, but also reports its association with centromeres; the copy does not establish that it lacks kinetochore and centromere localization domains. The cited review does not report the stated overexpression experiment. (LLM, conf=0.75)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

The citation lists haven’t been fetched yet

References 89 · Cited by 154

Research works printed but not linked: 85

  1. [1]Mitchison TJ Kirschner MW Dynamic instability of microtubule growth Nature 1984 312 237 42 6504138
  2. [2]Belmont LD Hyman AA Sawin KE Mitchison TJ Real-time visualization of cell cycle dependent changes in microtubule dynamics in cytoplasmic extracts Cell 1990 62 579 89 2379239
  3. [3]Saxton WM Stemple DL Leslie RJ Salmon ED Zavortink M McIntosh JR Tubulin dynamics in cultured mammalian cells J Cell Biol 1984 99 2175 86 6501419 PMC2113582
  4. [4]Zhai Y Kronebusch PJ Simon PM Borisy GG Microtubule dynamics at the G2/M transition: Abrupt breakdown of cytoplasmic microtubules at nuclear envelope breakdown and implications for spindle morphogenesis J Cell Biol 1996 135 201 14 8858174 PMC2121030
  5. [5]Rusan NM Fagerstrom CJ Yvon AM Wadsworth P Cell cycle-dependent changes in microtubule dynamics in living cells expressing green fluorescent protein-alpha tubulin Mol Biol Cell 2001 12 971 80 11294900 PMC32280
  6. [6]Kwok BH Kapoor TM Microtubule flux: Drivers wanted Curr Opin Cell Biol 2007 19 36 42 17174541
  7. [7]Mitchison TJ Polewards microtubule flux in the mitotic spindle: Evidence from photoactivation of fluorescence J Cell Biol 1989 109 637 52 2760109 PMC2115701
  8. [8]Rogers GC Rogers SL Sharp DJ Spindle microtubules in flux J Cell Sci 2005 118 1105 16 15764594
  9. [9]Mitchison TJ Salmon ED Poleward kinetochore fiber movement occurs during both metaphase and anaphase-A in newt lung cell mitosis J Cell Biol 1992 119 569 82 1400593 PMC2289668
  10. [10]Desai A Maddox PS Mitchison TJ Salmon ED Anaphase A chromosome movement and poleward spindle microtubule flux occur at similar rates in Xenopus extract spindles J Cell Biol 1998 141 703 13 9566970 PMC2132746
  11. [11]Rogers GC Rogers SL Schwimmer TA Ems-McClung SC Walczak CE Vale RD Two mitotic kinesins cooperate to drive sister chromatid separation during anaphase Nature 2004 427 364 70 14681690
  12. [12]Ganem NJ Upton K Compton DA Efficient mitosis in human cells lacking poleward microtubule flux Curr Biol 2005 15 1827 32 16243029
  13. [13]Matos I Pereira AJ Lince-Faria M Cameron LA Salmon ED Maiato H Synchronizing chromosome segregation by flux-dependent force equalization at kinetochores J Cell Biol 2009 186 11 26 19581410 PMC2712998
  14. [14]Desai A Verma S Mitchison TJ Walczak CE Kin I kinesins are microtubule-destabilizing enzymes Cell 1999 96 69 78 9989498
  15. [15]Sproul LR Anderson DJ Mackey AT Saunders WS Gilbert SP Cik1 targets the minus-end kinesin depolymerase Kar3 to microtubule plus ends Curr Biol 2005 15 1420 7 16085496 PMC2386176
  16. [16]Chu HM Yun M Anderson DE Sage H Park HW Endow SA Kar3 interaction with Cik1 alters motor structure and function EMBO J 2005 24 3214 23 16107877 PMC1224680
  17. [17]Gupta ML Jr Carvalho P Roof DM Pellman D Plus end-specific depolymerase activity of Kip3, a Kinesin-8 protein, explains its role in positioning the yeast mitotic spindle Nat Cell Biol 2006 8 913 23 16906148
  18. [18]Varga V Helenius J Tanaka K Hyman AA Tanaka TU Howard J Yeast Kinesin-8 depolymerizes microtubules in a length-dependent manner Nat Cell Biol 2006 8 957 62 16906145
  19. [19]Lawrence CJ Dawe RK Christie KR Cleveland DW Dawson SC Endow SA A standardized kinesin nomenclature J Cell Biol 2004 167 19 22 15479732 PMC2041940
  20. [20]Miki H Okada Y Hirokawa N Analysis of the kinesin superfamily: Insights into structure and function Trends Cell Biol 2005 15 467 76 16084724
  21. [21]Kim AJ Endow SA A kinesin family tree J Cell Sci 2000 113 3681 2 11034894
  22. [22]Wickstead B Gull K A “holistic” kinesin phylogeny reveals new kinesin families and predicts protein functions Mol Biol Cell 2006 17 1734 43 16481395 PMC1415282
  23. [23]Hunter AW Caplow M Coy DL Hancock WO Diez S Wordeman L The kinesin-related protein MCAK is a microtubule depolymerase that forms an ATP-hydrolyzing complex at microtubule ends Mol Cell 2003 11 445 57 12620232 PMC6468321
  24. [24]Helenius J Brouhard G Kalaidzidis Y Diez S Howard J The depolymerizing kinesin MCAK uses lattice diffusion to rapidly target microtubule ends Nature 2006 441 115 9 16672973
  25. [26]Wordeman L Wagenbach M Maney T Mutations in the ATP-binding domain affect the subcellular distribution of mitotic centromere-associated kinesin (MCAK) Cell Biol Int 1999 23 275 86 10600236
  26. [27]Maney T Hunter AW Wagenbach M Wordeman L Mitotic centromere-associated kinesin is important for anaphase chromosome segregation J Cell Biol 1998 142 787 801 9700166 PMC2148171
  27. [28]Walczak CE Gan EC Desai A Mitchison TJ Kline-Smith SL The microtubule-destabilizing kinesin XKCM1 is required for chromosome positioning during spindle assembly Curr Biol 2002 12 1885 9 12419191
  28. [29]Ovechkina Y Wagenbach M Wordeman L K-loop insertion restores microtubule depolymerizing activity of a “neckless” MCAK mutant J Cell Biol 2002 159 557 62 12446739 PMC2173087
  29. [30]Andrews PD Ovechkina Y Morrice N Wagenbach M Duncan K Wordeman L Aurora B regulates MCAK at the mitotic centromere Dev Cell 2004 6 253 68 14960279
  30. [31]Lan W Zhang X Kline-Smith SL Rosasco SE Barrett-Wilt GA Shabanowitz J Aurora B phosphorylates centromeric MCAK and regulates its localization and microtubule depolymerization activity Curr Biol 2004 14 273 86 14972678
  31. [32]Ohi R Sapra T Howard J Mitchison TJ Differentiation of cytoplasmic and meiotic spindle assembly MCAK functions by Aurora B-dependent phosphorylation Mol Biol Cell 2004 15 2895 906 15064354 PMC420112
  32. [33]Niederstasser H Salehi-Had H Gan EC Walczak C Nogales E XKCM1 acts on a single protofilament and requires the C terminus of tubulin J Mol Biol 2002 316 817 28 11866534
  33. [34]Ogawa T Nitta R Okada Y Hirokawa N A common mechanism for microtubule destabilizers – M type kinesins curl the protofilament using the class-specific neck and loops Cell 2004 116 591 602 14980225
  34. [35]Shipley K Hekmat-Nejad M Turner J Moores C Anderson R Milligan R Structure of a kinesin microtubule depolymerization machine EMBO J 2004 23 1422 32 15029249 PMC391071
  35. [36]Hertzer KM Ems-McClung SC Kline-Smith SL Lipkin TG Gilbert SP Walczak CE Full-length dimeric MCAK is a more efficient microtubule depolymerase than minimal domain monomeric MCAK Mol Biol Cell 2006 17 700 10 16291860 PMC1356581
  36. [37]Maney T Wagenbach M Wordeman L Molecular dissection of the microtubule depolymerizing activity of mitotic centromere-associated kinesin J Biol Chem 2001 276 34753 8 11466324
  37. [38]Aizawa H Sekine Y Takemura R Zhang Z Nangaku M Hirokawa N Kinesin family in murine central nervous system J Cell Biol 1992 119 1287 96 1447303 PMC2289715
  38. [39]Noda Y Sato-Yoshitake R Kondo S Nangaku M Hirokawa N KIF2 is a new microtubule-based anterograde motor that transports membranous organelles distinct from those carried by kinesin heavy chain or KIF3A/B J Cell Biol 1995 129 157 67 7535303 PMC2120367
  39. [40]Homma N Takei Y Tanaka Y Nakata T Terada S Kikkawa M Kinesin superfamily protein 2A (KIF2A) functions in suppression of collateral branch extension Cell 2003 114 229 39 12887924
  40. [41]Morfini G Quiroga S Rosa A Kosik K Caceres A Suppression of KIF2 in PC12 cells alters the distribution of a growth cone nonsynaptic membrane receptor and inhibits neurite extension J Cell Biol 1997 138 657 69 9245793 PMC2141628
  41. [43]Wordeman L Mitchison TJ Identification and partial characterization of mitotic centromere-associated kinesin, a kinesin-related protein that associates with centromeres during mitosis J Cell Biol 1995 128 95 104 7822426 PMC2120339
  42. [44]Gaetz J Kapoor TM Dynein/dynactin regulate metaphase spindle length by targeting depolymerizing activities to spindle poles J Cell Biol 2004 166 465 71 15314063 PMC1401226
  43. [45]Ganem NJ Compton DA The KinI kinesin Kif2a is required for bipolar spindle assembly through a functional relationship with MCAK J Cell Biol 2004 166 473 8 15302853 PMC2172212
  44. [46]Ohi R Burbank K Liu Q Mitchison TJ Nonredundant functions of Kinesin-13s during meiotic spindle assembly Curr Biol 2007 17 953 9 17509883
  45. [47]Cameron LA Yang G Cimini D Canman JC Kisurina-Evgenieva O Khodjakov A Kinesin 5-independent poleward flux of kinetochore microtubules in PtK1 cells J Cell Biol 2006 173 173 9 16636143 PMC2063808
  46. [48]Manning AL Ganem NJ Bakhoum SF Wagenbach M Wordeman L Compton DA The Kinesin-13 proteins Kif2a, Kif2b, and Kif2c/MCAK have distinct roles during mitosis in human cells Mol Biol Cell 2007 18 2970 9 17538014 PMC1949365
  47. [49]Walczak CE Mitchison TJ Desai A XKCM1: A Xenopus kinesin-related protein that regulates microtubule dynamics during mitotic spindle assembly Cell 1996 84 37 47 8548824
  48. [50]Goshima G Vale RD The roles of microtubule-based motor proteins in mitosis: comprehensive RNAi analysis in the Drosophila S2 cell line J Cell Biol 2003 162 1003 16 12975346 PMC2172859
  49. [51]Zhu C Zhao J Bibikova M Leverson JD Bossy-Wetzel E Fan JB Functional analysis of human microtubule-based motor proteins, the kinesins and dyneins, in mitosis/cytokinesis using RNA interference Mol Biol Cell 2005 16 3187 99 15843429 PMC1165403
  50. [52]Cassimeris L Morabito J TOGp, the human homolog of XMAP215/Dis1, is required for centrosome integrity, spindle pole organization, and bipolar spindle assembly Mol Biol Cell 2004 15 1580 90 14718566 PMC379257
  51. [53]Holmfeldt P Stenmark S Gullberg M Differential functional interplay of TOGp/XMAP215 and the KinI kinesin MCAK during interphase and mitosis EMBO J 2004 23 627 37 14749730 PMC1271808
  52. [54]Holmfeldt P Zhang X Stenmark S Walczak CE Gullberg M CaMKIIgamma-mediated inactivation of the Kin I kinesin MCAK is essential for bipolar spindle formation EMBO J 2005 24 1256 66 15775983 PMC556404
  53. [55]Kline-Smith SL Walczak CE The microtubule-destabilizing kinesin XKCM1 regulates microtubule dynamic instability in cells Mol Biol Cell 2002 13 2718 31 12181341 PMC117937
  54. [56]Stout JR Rizk RS Kline SL Walczak CE Deciphering protein function during mitosis in PtK cells using RNAi BMC Cell Biol 2006 7 26 16796742 PMC1559611
  55. [57]Toso A Winter JR Garrod AJ Amaro AC Meraldi P McAinsh AD Kinetochore-generated pushing forces separate centrosomes during bipolar spindle assembly J Cell Biol 2009 184 365 72 19204145 PMC2646558
  56. [58]Morales-Mulia S Scholey JM Spindle pole organization in Drosophila S2 cells by dynein, abnormal spindle protein (Asp), and KLP10A Mol Biol Cell 2005 16 3176 86 15888542 PMC1165402
  57. [59]Buster DW Zhang D Sharp DJ Poleward tubulin flux in spindles: regulation and function in mitotic cells Mol Biol Cell 2007 18 3094 104 17553931 PMC1949370
  58. [60]Rizk RS Bohannon KP Wetzel LA Powers J Shaw SL Walczak CE MCAK and paclitaxel have differential effects on spindle microtubule organization and dynamics Mol Biol Cell 2009 20 1639 51 19158381 PMC2655246
  59. [61]Wordeman L Wagenbach M von Dassow G MCAK facilitates chromosome movement by promoting kinetochore microtubule turnover J Cell Biol 2007 179 869 79 18039936 PMC2099197
  60. [62]Bakhoum SF Thompson SL Manning AL Compton DA Genome stability is ensured by temporal control of kinetochore-microtubule dynamics Nat Cell Biol 2009 11 27 35 19060894 PMC2614462
  61. [63]Kline-Smith SL Khodjakov A Hergert P Walczak CE Depletion of centromeric MCAK leads to chromosome congression and segregation defects due to improper kinetochore attachments Mol Biol Cell 2004 15 1146 59 14699064 PMC363095
  62. [64]Hedrick DG Stout JR Walczak CE Effects of anti-microtubule agents on microtubule organization in cells lacking the Kinesin-13 MCAK Cell Cycle 2008 7 2146 56 18635958
  63. [65]Brust-Mascher I Civelekoglu-Scholey G Kwon M Mogilner A Scholey JM Model for anaphase B: role of three mitotic motors in a switch from poleward flux to spindle elongation Proc Natl Acad Sci U S A 2004 101 15938 43 15522967 PMC524698
  64. [66]Laycock JE Savoian MS Glover DM Antagonistic activities of Klp10A and Orbit regulate spindle length, bipolarity and function in vivo J Cell Sci 2006 119 2354 61 16723741
  65. [67]Waters JC Mitchison TJ Rieder CL Salmon ED The kinetochore microtubule minus-end disassembly associated with poleward flux produces a force that can do work Mol Biol Cell 1996 7 1547 58 8898361 PMC276005
  66. [68]Zhang X Lan W Ems-McClung SC Stukenberg PT Walczak CE Aurora B phosphorylates multiple sites on mitotic centromere-associated kinesin to spatially and temporally regulate its function Mol Biol Cell 2007 18 3264 76 17567953 PMC1951741
  67. [69]Ems-McClung SC Hertzer KM Zhang X Miller MW Walczak CE The interplay of the N-and C-terminal domains of MCAK control microtubule depolymerization activity and spindle assembly Mol Biol Cell 2007 18 282 94 17093055 PMC1751331
  68. [70]Knowlton AL Vorozhko VV Lan W Gorbsky GJ Stukenberg PT ICIS and Aurora B coregulate the microtubule depolymerase Kif2a Curr Biol 2009 PMC2775053 19327998
  69. [71]Ohi R Coughlin ML Lane WS Mitchison TJ An inner centromere protein that stimulates the microtubule depolymerizing activity of a KinI kinesin Dev Cell 2003 5 309 21 12919681
  70. [72]Zhang X Ems-McClung SC Walczak CE Aurora A phosphorylates MCAK to control Ran-dependent spindle bipolarity Mol Biol Cell 2008 19 2752 65 18434591 PMC2441684
  71. [74]Katayama H Sasai K Kloc M Brinkley BR Sen S Aurora kinase-A regulates kinetochore/chromatin associated microtubule assembly in human cells Cell Cycle 2008 7 2691 704 18773538
  72. [75]Knowlton AL Lan W Stukenberg PT Aurora B is enriched at merotelic attachment sites, where it regulates MCAK Curr Biol 2006 16 1705 10 16950107
  73. [76]Xue Y Zhou F Zhu M Ahmed K Chen G Yao X GPS: a comprehensive www server for phosphorylation sites prediction Nucleic Acids Res 2005 33 W184 7 15980451 PMC1160154
  74. [77]DeLuca M Brunetto L Asteriti IA Giubettini M Lavia P Guarguaglini G Aurora-A and ch-TOG act in a common pathway in control of spindle pole integrity Oncogene 2008 27 6539 49 18663358
  75. [78]Jang CY Wong J Coppinger JA Seki A Yates JR 3rd Fang G DDA3 recruits microtubule depolymerase Kif2a to spindle poles and controls spindle dynamics and mitotic chromosome movement J Cell Biol 2008 181 255 67 18411309 PMC2315673
  76. [79]Banks JD Heald R Adenomatous polyposis coli associates with the microtubule-destabilizing protein XMCAK Curr Biol 2004 14 2033 8 15556866
  77. [80]Barth AI Caro-Gonzalez HY Nelson WJ Role of adenomatous polyposis coli (APC) and microtubules in directional cell migration and neuronal polarization Semin Cell Dev Biol 2008 19 245 51 18387324 PMC2673958
  78. [81]Rusan NM Peifer M Original CIN: Reviewing roles for APC in chromosome instability J Cell Biol 2008 181 719 26 18519734 PMC2396796
  79. [82]Dikovskaya D Newton IP Nathke IS The adenomatous polyposis coli protein is required for the formation of robust spindles formed in CSF Xenopus extracts Mol Biol Cell 2004 15 2978 91 15075372 PMC420119
  80. [83]Lee T Langford KJ Askham JM Bruning-Richardson A Morrison EE MCAK associates with EB1 Oncogene 2008 27 2494 500 17968321
  81. [84]Su LK Burrell M Hill DE Gyuris J Brent R Wiltshire R APC binds to the novel protein EB1 Cancer Res 1995 55 2972 7 7606712
  82. [85]Mimori-Kiyosue Y Shiina N Tsukita S The dynamic behavior of the APC-binding protein EB1 on the distal ends of microtubules Curr Biol 2000 10 865 8 10899006
  83. [86]Niethammer P Kronja I Kandels-Lewis S Rybina S Bastiaens P Karsenti E Discrete states of a protein interaction network govern interphase and mitotic microtubule dynamics PLoS Biol 2007 5 e29 17227146 PMC1769425
  84. [88]Honnappa S Gouveia S Weisbrich A Damberger F Bhavesh N Jawhari H An EB1-binding motif acts as a microtubule tip localization signal Cell 2009 138 366 76 19632184
  85. [89]Jiang K Wang J Liu J Ward T Wordeman L Davidson A TIP150 interacts with and targets MCAK at the microtubule plus ends EMBO Rep 2009 PMC2699393 19543227

Authors
Ems-McClung, S. C., & Walczak, C. E.
Affiliations
Indiana University Bloomington (US)
Corresponding author
Walczak, Claire E.
ORCID
Venue
Seminars in Cell & Developmental Biology
Publisher
Elsevier BV
Published
2010-05
Volume
21
Issue
3
Pages
276-282
ISSN
1084-9521 (ISSN-L)
DOI
10.1016/j.semcdb.2010.01.016
PMC
PMC2844478
OpenAlex
W2028880495
Cited by
154
References
89
Citations by year
2026: 4 · 2025: 6 · 2024: 9 · 2023: 11 · 2022: 15 · 2021: 7 · 2020: 7 · 2019: 9 · 2018: 8 · 2017: 4 · 2016: 7 · 2015: 14 · 2014: 6 · 2013: 12 · 2012: 15
FWCI
6.58
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Seminars in Cell and Developmental Biology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institute of General Medical Sciences (GM059618, R01GM059618)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
  • Health Sciences › Medicine › Oncology › Cancer Treatment and Pharmacology
  • Physical Sciences › Chemistry › Organic Chemistry › Synthesis and biological activity
Keywords
kinesin-13, mitosis, spindle microtubules, microtubule dynamics, microtubule depolymerization, spindle assembly, kinetochore-microtubule attachment, phosphorylation regulation, protein-protein interaction
MeSH terms
Amino Acid Sequence, Animals, Chromosomes, Humans, Microtubules, Mitosis, Spindle Apparatus, Molecular Sequence Data, Phosphorylation, Xenopus, Kinesins, Sequence Homology, Amino Acid, Protein Structure, Tertiary, Protein Interaction Mapping

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review