Abstract
Cytoplasmic dynein is a large minus-end-directed microtubule motor complex, involved in many different cellular processes including intracellular trafficking, organelle positioning, and microtubule organization. Furthermore, dynein plays essential roles during cell division where it is implicated in multiple processes including centrosome separation, chromosome movements, spindle organization, spindle positioning, and mitotic checkpoint silencing. How is a single motor able to fulfill this large array of functions and how are these activities temporally and spatially regulated? The answer lies in the unique composition of the dynein motor and in the interactions it makes with multiple regulatory proteins that define the time and place where dynein becomes active. Here, we will focus on the different mitotic processes that dynein is involved in, and how its regulatory proteins act to support dynein. Although dynein is highly conserved amongst eukaryotes (with the exception of plants), there is significant variability in the cellular processes that depend on dynein in different species. In this review, we concentrate on the functions of cytoplasmic dynein in mammals but will also refer to data obtained in other model organisms that have contributed to our understanding of dynein function in higher eukaryotes.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Barisic M, Geley S (2011) Spindly switch controls anaphase: Spindly and RZZ functions in chromosome attachment and mitotic checkpoint control. Cell Cycle 10:449–456. doi:10.4161/cc.10.3.14759
Barisic M, Sohm B, Mikolcevic P et al (2010) Spindly/CCDC99 is required for efficient chromosome congression and mitotic checkpoint regulation. Mol Biol Cell 21:1968–1981. doi:10.1091/mbc.E09-04-0356
Basto R, Scaerou F, Mische S et al (2004) In vivo dynamics of the rough deal checkpoint protein during Drosophila mitosis. Curr Biol 14:56–61
Basto R, Brunk K, Vinadogrova T et al (2008) Centrosome amplification can initiate tumorigenesis in flies. Cell 133:1032–1042. doi:10.1016/j.cell.2008.05.039
Beaudouin J, Gerlich D, Daigle N et al (2002) Nuclear envelope breakdown proceeds by microtubule-induced tearing of the lamina. Cell 108:83–96
Bird SL, Heald R, Weis K (2013) RanGTP and CLASP1 cooperate to position the mitotic spindle. Mol Biol Cell 24:2506–2514. doi:10.1091/mbc.E13-03-0150
Blangy A, Lane HA, d’Herin P et al (1995) Phosphorylation by p34cdc2 regulates spindle association of human Eg5, a kinesin-related motor essential for bipolar spindle formation in vivo. Cell 83:1159–1169
Bolhy S, Bouhlel I, Dultz E et al (2011) A Nup133-dependent NPC-anchored network tethers centrosomes to the nuclear envelope in prophase. J Cell Biol 192:855–871. doi:10.1083/jcb.201007118
Braun M, Drummond DR, Cross RA, McAinsh AD (2009) The kinesin-14 Klp2 organizes microtubules into parallel bundles by an ATP-dependent sorting mechanism. Nat Cell Biol 11:724–730. doi:10.1038/ncb1878
Buffin E, Lefebvre C, Huang J et al (2005) Recruitment of Mad2 to the kinetochore requires the Rod/Zw10 complex. Curr Biol 15:856–861. doi:10.1016/j.cub.2005.03.052
Burkhardt JK, Echeverri CJ, Nilsson T, Vallee RB (1997) Overexpression of the dynamitin (p50) subunit of the dynactin complex disrupts dynein-dependent maintenance of membrane organelle distribution. J Cell Biol 139:469–484
Busson S, Dujardin D, Moreau A et al (1998) Dynein and dynactin are localized to astral microtubules and at cortical sites in mitotic epithelial cells. Curr Biol 8:541–544
Cai S, Weaver LN, Ems-McClung SC, Walczak CE (2009) Kinesin-14 family proteins HSET/XCTK2 control spindle length by cross-linking and sliding microtubules. Mol Biol Cell 20:1348–1359. doi:10.1091/mbc.E08-09-0971
Carter AP, Garbarino JE, Wilson-Kubalek EM et al (2008) Structure and functional role of dynein’s microtubule-binding domain. Science 322:1691–1695. doi:10.1126/science.1164424
Carter AP, Cho C, Jin L, Vale RD (2011) Crystal structure of the dynein motor domain. Science 331:1159–1165. doi:10.1126/science.1202393
Chan YW (2009) Mitotic control of kinetochore-associated dynein and spindle orientation by human Spindly. J Cell Biol 185:859–874. doi:10.1083/jcb.200812167.dv
Cho C, Vale RD (2012) The mechanism of dynein motility: insight from crystal structures of the motor domain. Biochim Biophys Acta 1823:182–191. doi:10.1016/j.bbamcr.2011.10.009
Collins ES, Balchand SK, Faraci JL et al (2012) Cell cycle-regulated cortical dynein/dynactin promotes symmetric cell division by differential pole motion in anaphase. Mol Biol Cell 23:3380–3390. doi:10.1091/mbc.E12-02-0109
Courtois A, Schuh M, Ellenberg J, Hiiragi T (2012) The transition from meiotic to mitotic spindle assembly is gradual during early mammalian development. J Cell Biol 198:357–370. doi:10.1111/j.1600-0854.2009.00945.x
Couwenbergs C, Labbé J-C, Goulding M et al (2007) Heterotrimeric G protein signaling functions with dynein to promote spindle positioning in C. elegans. J Cell Biol 179:15–22. doi:10.1083/jcb.200707085
Culver-Hanlon TL, Lex SA, Stephens AD et al (2006) A microtubule-binding domain in dynactin increases dynein processivity by skating along microtubules. Nat Cell Biol 8:264–270
DeWitt MA, Chang AY, Combs PA, Yildiz A (2012) Cytoplasmic dynein moves through uncoordinated stepping of the AAA+ ring domains. Science 335:221–225. doi:10.1126/science.1215804
Du Q, Macara IG (2004) Mammalian Pins is a conformational switch that links NuMA to heterotrimeric G proteins. Cell 119:503–516. doi:10.1016/j.cell.2004.10.028
Du Q, Taylor L, Compton DA, Macara IG (2002) LGN blocks the ability of NuMA to bind and stabilize microtubules. A mechanism for mitotic spindle assembly regulation. Curr Biol 12:1928–1933
Echeverri CJ, Paschal BM, Vaughan KT, Vallee RB (1996) Molecular characterization of the 50-kD subunit of dynactin reveals function for the complex in chromosome alignment and spindle organization during mitosis. J Cell Biol 132:617–633
Efimov VP (2003) Roles of NUDE and NUDF proteins of Aspergillus nidulans: insights from intracellular localization and overexpression effects. Mol Biol Cell 14:871–888. doi:10.1091/mbc.E02-06-0359
Efimov VP, Morris NR (2000) The LIS1-related NUDF protein of Aspergillus nidulans interacts with the coiled-coil domain of the NUDE/RO11 protein. J Cell Biol 150:681–688
Endow SA, Chandra R, Komma DJ et al (1994) Mutants of the Drosophila ncd microtubule motor protein cause centrosomal and spindle pole defects in mitosis. J Cell Sci 107(Pt 4):859–867
Fant X, Merdes A, Haren L (2004) Cell and molecular biology of spindle poles and NuMA. Int Rev Cytol 238:1–57. doi:10.1016/S0074-7696(04)38001-0
Ferenz NP, Paul R, Fagerstrom C et al (2009) Dynein antagonizes eg5 by crosslinking and sliding antiparallel microtubules. Curr Biol 19:1833–1838. doi:10.1016/j.cub.2009.09.025
Fink G, Schuchardt I, Colombelli J et al (2006) Dynein-mediated pulling forces drive rapid mitotic spindle elongation in Ustilago maydis. EMBO J 25:4897–4908. doi:10.1038/sj.emboj.7601354
Fink G, Hajdo L, Skowronek KJ et al (2009) The mitotic kinesin-14 Ncd drives directional microtubule-microtubule sliding. Nat Cell Biol 11:717–723. doi:10.1038/ncb1877
Fink J, Carpi N, Betz T et al (2011) External forces control mitotic spindle positioning. Nat Cell Biol 13:771–778. doi:10.1038/ncb2269
Firestone AJ, Weinger JS, Maldonado M et al. (2012) Small-molecule inhibitors of the AAA+ ATPase motor cytoplasmic dynein. Nature 1–5. doi:10.1038/nature10936
Foisner R, Gerace L (1993) Integral membrane proteins of the nuclear envelope interact with lamins and chromosomes, and binding is modulated by mitotic phosphorylation. Cell 73:1267–1279
Gaetz J, Kapoor TM (2004) Dynein/dynactin regulate metaphase spindle length by targeting depolymerizing activities to spindle poles. J Cell Biol 166:465–471. doi:10.1083/jcb.200404015
Gaglio T, Saredi A, Compton DA (1995) NuMA is required for the organization of microtubules into aster-like mitotic arrays. J Cell Biol 131:693–708
Gaglio T, Saredi A, Bingham JB et al (1996) Opposing motor activities are required for the organization of the mammalian mitotic spindle pole. J Cell Biol 135:399–414
Gaglio T, Dionne MA, Compton DA (1997) Mitotic spindle poles are organized by structural and motor proteins in addition to centrosomes. J Cell Biol 138:1055–1066
Galli M, van den Heuvel S (2008) Determination of the cleavage plane in early C. elegans embryos. Annu Rev Genet 42:389–411. doi:10.1146/annurev.genet.40.110405.090523
Gassmann R, Essex A, Hu JS et al (2008) A new mechanism controlling kinetochore-microtubule interactions revealed by comparison of two dynein-targeting components: SPDL-1 and the Rod/Zwilch/Zw10 complex. Genes Dev 22:2385–2399
Gassmann R, Holland AJ, Varma D et al (2010) Removal of Spindly from microtubule-attached kinetochores controls spindle checkpoint silencing in human cells. Genes Dev 24:957–971. doi:10.1101/gad.1886810
Gennerich A, Carter AP, Reck-Peterson SL, Vale RD (2007) Force-induced bidirectional stepping of cytoplasmic dynein. Cell 131:952–965. doi:10.1016/j.cell.2007.10.016
Georgatos SD, Pyrpasopoulou A, Theodoropoulos PA (1997) Nuclear envelope breakdown in mammalian cells involves stepwise lamina disassembly and microtubule-drive deformation of the nuclear membrane. J Cell Sci 110(Pt 17):2129–2140
Gibbons IR, Rowe AJ (1965) Dynein: a protein with adenosine triphosphatase activity from cilia. Science 149:424–426. doi:10.1126/science.149.3682.424
Gonczy P, Pichler S, Kirkham M, Hyman AA (1999) Cytoplasmic dynein is required for distinct aspects of MTOC positioning, including centrosome separation, in the one cell stage Caenorhabditis elegans embryo. J Cell Biol 147:135–150
Goshima G, Nedelec F, Vale RD (2005) Mechanisms for focusing mitotic spindle poles by minus end-directed motor proteins. J Cell Biol 171:229–240
Griffis ER, Stuurman N, Vale RD (2007) Spindly, a novel protein essential for silencing the spindle assembly checkpoint, recruits dynein to the kinetochore. J Cell Biol 177:1005–1015. doi:10.1083/jcb.200702062
Gudimchuk N, Vitre B, Kim Y et al (2013) Kinetochore kinesin CENP-E is a processive bi-directional tracker of dynamic microtubule tips. Nat Cell Biol 15:1079–1088. doi:10.1038/ncb2831
Hammesfahr BR, Kollmar M (2012) Evolution of the eukaryotic dynactin complex, the activator of cytoplasmic dynein. BMC Evol Biol 12:1–1. doi:10.1186/1471-2148-12-95
Heald R, Tournebize R, Blank T et al (1996) Self-organization of microtubules into bipolar spindles around artificial chromosomes in Xenopus egg extracts. Nature 382:420–425. doi:10.1038/382420a0
Heald R, Tournebize R, Habermann A et al (1997) Spindle assembly in Xenopus egg extracts: respective roles of centrosomes and microtubule self-organization. J Cell Biol 138:615–628
Hebbar S, Mesngon MT, Guillotte AM et al (2008) Lis1 and Ndel1 influence the timing of nuclear envelope breakdown in neural stem cells. J Cell Biol 182:1063–1071. doi:10.1083/jcb.200803071
Hoffman DB, Pearson CG, Yen TJ et al (2001) Microtubule-dependent changes in assembly of microtubule motor proteins and mitotic spindle checkpoint proteins at PtK1 kinetochores. Mol Biol Cell 12:1995–2009
Howell BJ, Hoffman DB, Fang G et al (2000) Visualization of Mad2 dynamics at kinetochores, along spindle fibers, and at spindle poles in living cells. J Cell Biol 150:1233–1250
Howell BJ, McEwen BF, Canman JC et al (2001) Cytoplasmic dynein/dynactin drives kinetochore protein transport to the spindle poles and has a role in mitotic spindle checkpoint inactivation. J Cell Biol 155:1159–1172. doi:10.1083/jcb.200105093
Hoyt MA, He L, Totis L, Saunders WS (1993) Loss of function of Saccharomyces cerevisiae kinesin-related CIN8 and KIP1 is suppressed by KAR3 motor domain mutations. Genetics 135:35–44
Hu DJ-K, Baffet AD, Nayak T et al (2013) Dynein recruitment to nuclear pores activates apical nuclear migration and mitotic entry in brain progenitor cells. Cell 154:1300–1313. doi:10.1016/j.cell.2013.08.024
Huang J, Roberts AJ, Leschziner AE, Reck-Peterson SL (2012) Lis1 Acts as a “Clutch” between the ATPase and microtubule-binding domains of the dynein motor. Cell 150:975–986. doi:10.1016/j.cell.2012.07.022
Inaba M, Yamashita YM (2012) Asymmetric stem cell division: precision for robustness. Stem Cell 11:461–469. doi:10.1016/j.stem.2012.09.003
Jelluma N, Dansen TB, Sliedrecht T et al (2010) Release of Mps1 from kinetochores is crucial for timely anaphase onset. J Cell Biol 191:281–290. doi:10.1083/jcb.201003038
Kapitein LC, Peterman EJ, Kwok BH et al (2005) The bipolar mitotic kinesin Eg5 moves on both microtubules that it crosslinks. Nature 435:114–118
Kardon JR, Vale RD (2009) Regulators of the cytoplasmic dynein motor. Nat Rev Mol Cell Biol 10:854–865. doi:10.1038/nrm2804
Karess R (2005) Rod-Zw10-Zwilch: a key player in the spindle checkpoint. Trends Cell Biol 15:386–392
Karess RE, Glover DM (1989) rough deal: a gene required for proper mitotic segregation in Drosophila. J Cell Biol 109:2951–2961
Kashina AS, Baskin RJ, Cole DG et al (1996) A bipolar kinesin. Nature 379:270–272
Khodjakov A (2003) Minus-end capture of preformed kinetochore fibers contributes to spindle morphogenesis. J Cell Biol 160:671–683. doi:10.1083/jcb.200208143
Khodjakov A, Cole RW, Oakley BR, Rieder CL (2000) Centrosome-independent mitotic spindle formation in vertebrates. Curr Biol 10:59–67
Kikkawa M (2013) Big steps toward understanding dynein. J Cell Biol 202:15–23. doi:10.1073/pnas.90.17.7928
Kim AJ, Endow SA (2000) A kinesin family tree. J Cell Sci 113(Pt 21):3681–3682
Kim H, Ling SC, Rogers GC et al (2007) Microtubule binding by dynactin is required for microtubule organization but not cargo transport. J Cell Biol 176:641–651
King SJ, Schroer TA (2000) Dynactin increases the processivity of the cytoplasmic dynein motor. Nat Cell Biol 2:20–24
King SM, Haley BE, Witman GB (1989) Structure of the alpha and beta heavy chains of the outer arm dynein from Chlamydomonas flagella. Nucleotide binding sites. J Biol Chem 264:10210–10218
King JM, Hays TS, Nicklas RB (2000) Dynein is a transient kinetochore component whose binding is regulated by microtubule attachment, not tension. J Cell Biol 151:739–748
Kiyomitsu T, Cheeseman IM (2012) Chromosome- and spindle-pole-derived signals generate an intrinsic code for spindle position and orientation. Nat Cell Biol 14:311–317. doi:10.1038/ncb2440
Kiyomitsu T, Cheeseman IM (2013) Cortical dynein and asymmetric membrane elongation coordinately position the spindle in anaphase. Cell 154:391–402. doi:10.1016/j.cell.2013.06.010
Kleylein-Sohn J, Pöllinger B, Ohmer M et al (2012) Acentrosomal spindle organization renders cancer cells dependent on the kinesin HSET. J Cell Sci 125:5391–5402. doi:10.1242/jcs.107474
Knoblich JA (2008) Mechanisms of asymmetric stem cell division. Cell 132:583–597. doi:10.1016/j.cell.2008.02.007
Knoblich JA (2010) Asymmetric cell division: recent developments and their implications for tumour biology. Nat Rev Mol Cell Biol 11:849–860. doi:10.1038/nrm3010
Kon T, Nishiura M, Ohkura R et al (2004) Distinct functions of nucleotide-binding/hydrolysis sites in the four AAA modules of cytoplasmic dynein. Biochemistry 43:11266–11274. doi:10.1021/bi048985a
Kon T, Imamula K, Roberts AJ et al (2009) Helix sliding in the stalk coiled coil of dynein couples ATPase and microtubule binding. Nat Struct Mol Biol 16:325–333. doi:10.1038/nsmb.1555
Kops GJ, Kim Y, Weaver BA et al (2005) ZW10 links mitotic checkpoint signaling to the structural kinetochore. J Cell Biol 169:49–60. doi:10.1083/jcb.200411118
Kotak S, Busso C, Gonczy P (2012) Cortical dynein is critical for proper spindle positioning in human cells. J Cell Biol 199:97–110. doi:10.1083/jcb.201203166
Kotak S, Busso C, Gonczy P (2013) NuMA phosphorylation by CDK1 couples mitotic progression with cortical dynein function. EMBO J 1–13. doi:10.1038/emboj.2013.172
Kuijt TEF, Omerzu M, Saurin AT, Kops GJPL (2014) Conditional targeting of MAD1 to kinetochores is sufficient to reactivate the spindle assembly checkpoint in metaphase. Chromosoma. doi:10.1007/s00412-014-0458-9
Kwon M, Godinho SA, Chandhok NS et al (2008) Mechanisms to suppress multipolar divisions in cancer cells with extra centrosomes. Genes Dev 22:2189–2203. doi:10.1101/gad.1700908
Laan L, Pavin N, Husson J et al (2012) Cortical dynein controls microtubule dynamics to generate pulling forces that position microtubule asters. Cell 148:502–514. doi:10.1016/j.cell.2012.01.007
Lam C, Vergnolle MAS, Thorpe L et al (2010) Functional interplay between LIS1, NDE1 and NDEL1 in dynein-dependent organelle positioning. J Cell Sci 123:202–212. doi:10.1242/jcs.059337
Li R (2013) The art of choreographing asymmetric cell division. Dev Cell 25:439–450. doi:10.1016/j.devcel.2013.05.003
Li Y, Yu W, Liang Y, Zhu X (2007) Kinetochore dynein generates a poleward pulling force to facilitate congression and full chromosome alignment. Cell Res 17:701–712. doi:10.1038/cr.2007.65
Lombillo VA, Stewart RJ, McIntosh JR (1995) Minus-end-directed motion of kinesin-coated microspheres driven by microtubule depolymerization. Nature 373:161–164. doi:10.1038/373161a0
Lye RJ, Porter ME, Scholey JM, McIntosh JR (1987) Identification of a microtubule-based cytoplasmic motor in the nematode C. elegans. Cell 51:309–318
Maiato H, Lince-Faria M (2010) The perpetual movements of anaphase. Cell Mol Life Sci 67:2251–2269. doi:10.1007/s00018-010-0327-5
Maiato H, Rieder CL, Khodjakov A (2004) Kinetochore-driven formation of kinetochore fibers contributes to spindle assembly during animal mitosis. J Cell Biol 167:831–840
Maldonado M, Kapoor TM (2011) Constitutive Mad1 targeting to kinetochores uncouples checkpoint signalling from chromosome biorientation. Nat Cell Biol 13:475–482. doi:10.1038/ncb2223
Manning AL, Compton DA (2007) Mechanisms of spindle-pole organization are influenced by kinetochore activity in mammalian cells. Curr Biol 17:260–265. doi:10.1016/j.cub.2006.11.071
McIntosh JR, Grishchuk EL, Morphew MK et al (2008) Fibrils connect microtubule tips with kinetochores: a mechanism to couple tubulin dynamics to chromosome motion. Cell 135:322–333. doi:10.1016/j.cell.2008.08.038
McKenney RJ, Vershinin M, Kunwar A et al (2010) LIS1 and NudE induce a persistent dynein force-producing state. Cell 141:304–314
McKenney RJ, Weil SJ, Scherer J, Vallee RB (2011) Mutually exclusive cytoplasmic dynein regulation by NudE-Lis1 and dynactin. J Biol Chem 286:39615–39622. doi:10.1074/jbc.M111.289017
Megraw TL, Kao LR, Kaufman TC (2001) Zygotic development without functional mitotic centrosomes. Curr Biol 11:116–120
Merdes A, van Haren L (2002) Direct binding of NuMA to tubulin is mediated by a novel sequence motif in the tail domain that bundles and stabilizes microtubules 1–10
Merdes A, Ramyar K, Vechio JD, Cleveland DW (1996) A complex of NuMA and cytoplasmic dynein is essential for mitotic spindle assembly. Cell 87:447–458
Merdes A, Heald R, Samejima K et al (2000) Formation of spindle poles by dynein/dynactin-dependent transport of NuMA. J Cell Biol 149:851–862
Mikami A, Tynan SH, Hama T et al (2002) Molecular structure of cytoplasmic dynein 2 and its distribution in neuronal and ciliated cells. J Cell Sci 115:4801–4808
Minke PF, Lee IH, Tinsley JH et al (1999) Neurospora crassa ro-10 and ro-11 genes encode novel proteins required for nuclear distribution. Mol Microbiol 32:1065–1076
Mitchison TJ, Maddox P, Gaetz J et al (2005) Roles of polymerization dynamics, opposed motors, and a tensile element in governing the length of Xenopus extract meiotic spindles. Mol Biol Cell 16:3064–3076. doi:10.1091/mbc.E05-02-0174
Mohri H (1968) Amino-acid composition of “Tubulin” constituting microtubules of sperm flagella. Nature 217:1053–1054
Morales-Mulia S, Scholey JM (2005) Spindle pole organization in Drosophila S2 cells by dynein, abnormal spindle protein (Asp), and KLP10A. Mol Biol Cell 16:3176–3186. doi:10.1091/mbc.E04-12-1110
Morin X, Bellaïche Y (2011) Mitotic spindle orientation in asymmetric and symmetric cell divisions during animal development. Dev Cell 21:102–119. doi:10.1016/j.devcel.2011.06.012
Mountain V, Simerly C, Howard L et al (1999) The kinesin-related protein, HSET, opposes the activity of Eg5 and cross-links microtubules in the mammalian mitotic spindle. J Cell Biol 147:351–366
Neuwald AF, Aravind L, Spouge JL, Koonin EV (1999) AAA+: a class of chaperone-like ATPases associated with the assembly, operation, and disassembly of protein complexes. Genome Res 9:27–43. doi:10.1101/gr.9.1.27
Nguyen-Ngoc T, Afshar K, Gönczy P (2007) Coupling of cortical dynein and G alpha proteins mediates spindle positioning in Caenorhabditis elegans. Nat Cell Biol 9:1294–1302. doi:10.1038/ncb1649
Nyarko A, Song Y, Barbar E (2012) Intrinsic disorder in dynein intermediate chain modulates its interactions with NudE and dynactin. J Biol Chem. doi:10.1074/jbc.M112.376038
O’Connell CB, Wang YL (2000) Mammalian spindle orientation and position respond to changes in cell shape in a dynein-dependent fashion. Mol Biol Cell 11:1765–1774
O’Connell MJ, Meluh PB, Rose MD, Morris NR (1993) Suppression of the bimC4 mitotic spindle defect by deletion of klpA, a gene encoding a KAR3-related kinesin-like protein in Aspergillus nidulans. J Cell Biol 120:153–162
Paschal BM, Shpetner HS, Vallee RB (1987) MAP 1C is a microtubule-activated ATPase which translocates microtubules in vitro and has dynein-like properties. J Cell Biol 105:1273–1282
Pfister KK (2005) Cytoplasmic dynein nomenclature. J Cell Biol 171:411–413. doi:10.1083/jcb.200508078
Qiu W, Derr ND, Goodman BS et al (2012) Dynein achieves processive motion using both stochastic and coordinated stepping. Nat Struct Mol Biol 19:193–200. doi:10.1038/nsmb.2205
Quintyne NJ, Gill SR, Eckley DM et al (1999) Dynactin is required for microtubule anchoring at centrosomes. J Cell Biol 147:321–334
Raaijmakers JA, van Heesbeen RGHP, Meaders JL et al (2012) Nuclear envelope-associated dynein drives prophase centrosome separation and enables Eg5-independent bipolar spindle formation. EMBO J 31:4179–4190. doi:10.1038/emboj.2012.272
Raaijmakers JA, Tanenbaum ME, Medema RH (2013) Systematic dissection of dynein regulators in mitosis. J Cell Biol 201:201–215. doi:10.1083/jcb.201208098
Reck-Peterson SL, Yildiz A, Carter AP et al (2006) Single-molecule analysis of dynein processivity and stepping behavior. Cell 126:335–348. doi:10.1016/j.cell.2006.05.046
Reddy AS, Day IS (2001) Kinesins in the Arabidopsis genome: a comparative analysis among eukaryotes. BMC Genomics 2:2
Reiner O, Carrozzo R, Shen Y et al (1993) Isolation of a Miller-Dieker lissencephaly gene containing G protein beta-subunit-like repeats. Nature 364:717–721. doi:10.1038/364717a0
Reis R, Feijão T, Gouveia S et al (2009) Dynein and mast/orbit/CLASP have antagonistic roles in regulating kinetochore-microtubule plus-end dynamics. J Cell Sci 122:2543–2553. doi:10.1242/jcs.044818
Robbins E, Gonatas NK (1964) The ultrastructure of a mammalian cell during the mitotic cycle. J Cell Biol 21:429–463
Roberts AJ, Kon T, Knight PJ et al. (2013) Functions and mechanics of dynein motor proteins. Nat Rev Mol Cell Biol 1–14. doi:10.1038/nrm3667
Robinson JT, Wojcik EJ, Sanders MA et al (1999) Cytoplasmic dynein is required for the nuclear attachment and migration of centrosomes during mitosis in Drosophila. J Cell Biol 146:597–608
Ross JL, Wallace K, Shuman H et al (2006) Processive bidirectional motion of dynein-dynactin complexes in vitro. Nat Cell Biol 8:562–570. doi:10.1038/ncb1421
Rusan NM, Tulu US, Fagerstrom C, Wadsworth P (2002) Reorganization of the microtubule array in prophase/prometaphase requires cytoplasmic dynein-dependent microtubule transport. J Cell Biol 158:997–1003. doi:10.1083/jcb.200204109
Salina D, Bodoor K, Eckley DM et al (2002) Cytoplasmic dynein as a facilitator of nuclear envelope breakdown. Cell 108:97–107
Saunders WS, Koshland D, Eshel D et al (1995) Saccharomyces cerevisiae kinesin- and dynein-related proteins required for anaphase chromosome segregation. J Cell Biol 128:617–624
Schmidt DJ, Rose DJ, Saxton WM, Strome S (2005) Functional analysis of cytoplasmic dynein heavy chain in Caenorhabditis elegans with fast-acting temperature-sensitive mutations. Mol Biol Cell 16:1200–1212. doi:10.1091/mbc.E04-06-0523
Schroer TA (2004) Dynactin. Annu Rev Cell Dev Biol 20:759–779. doi:10.1146/annurev.cellbio.20.012103.094623
Schroer TA, Sheetz MP (1991) Two activators of microtubule-based vesicle transport. J Cell Biol 115:1309–1318
Seldin L, Poulson ND, Foote HP, Lechler T (2013) NuMA localization, stability and function in spindle orientation involves 4.1 and Cdk1 interactions. Mol Biol Cell. doi:10.1091/mbc.E13-05-0277
Sharp DJ, Yu KR, Sisson JC et al (1999) Antagonistic microtubule-sliding motors position mitotic centrosomes in Drosophila early embryos. Nat Cell Biol 1:51–54
Sharp DJ, Brown HM, Kwon M et al (2000a) Functional coordination of three mitotic motors in Drosophila embryos. Mol Biol Cell 11:241–253
Sharp DJ, Rogers GC, Scholey JM (2000b) Cytoplasmic dynein is required for poleward chromosome movement during mitosis in Drosophila embryos. Nat Cell Biol 2:922–930. doi:10.1038/35046574
Silk AD, Holland AJ, Cleveland DW (2009) Requirements for NuMA in maintenance and establishment of mammalian spindle poles. J Cell Biol 184:677–690
Siller KH, Doe CQ (2009) Spindle orientation during asymmetric cell division. Nat Cell Biol 11:365–374. doi:10.1038/ncb0409-365
Splinter D, Tanenbaum ME, Lindqvist A et al. (2010) Bicaudal D2, dynein, and kinesin-1 associate with nuclear pore complexes and regulate centrosome and nuclear positioning during mitotic entry. 8:e1000350. doi:10.1371/journal.pbio.1000350
Splinter D, Razafsky DS, Schlager MA et al (2012) BICD2, dynactin, and LIS1 cooperate in regulating dynein recruitment to cellular structures. Mol Biol Cell 23:4226–4241. doi:10.1091/mbc.E12-03-0210
Starr DA, Williams BC, Hays TS, Goldberg ML (1998) ZW10 helps recruit dynactin and dynein to the kinetochore. J Cell Biol 142:763–774
Starr DA, Saffery R, Li Z et al (2000) HZwint-1, a novel human kinetochore component that interacts with HZW10. J Cell Sci 113(Pt 11):1939–1950
Stehman SA, Chen Y, McKenney RJ, Vallee RB (2007) NudE and NudEL are required for mitotic progression and are involved in dynein recruitment to kinetochores. J Cell Biol 178:583–594. doi:10.1083/jcb.200610112
Tai CY, Dujardin DL, Faulkner NE, Vallee RB (2002) Role of dynein, dynactin, and CLIP-170 interactions in LIS1 kinetochore function. J Cell Biol 156:959–968. doi:10.1083/jcb.200109046
Tall GG, Gilman AG (2005) Resistance to inhibitors of cholinesterase 8A catalyzes release of Galphai-GTP and nuclear mitotic apparatus protein (NuMA) from NuMA/LGN/Galphai-GDP complexes. Proc Natl Acad Sci U S A 102:16584–16589. doi:10.1073/pnas.0508306102
Tanenbaum ME, Medema RH (2010) Mechanisms of centrosome separation and bipolar spindle assembly. Dev Cell 19:797–806. doi:10.1016/j.devcel.2010.11.011
Tanenbaum ME, Macurek L, Galjart N, Medema RH (2008) Dynein, Lis1 and CLIP-170 counteract Eg5-dependent centrosome separation during bipolar spindle assembly. EMBO J 27:3235–3245. doi:10.1038/emboj.2008.242
Tanenbaum ME, Macurek L, Janssen A et al (2009) Kif15 cooperates with eg5 to promote bipolar spindle assembly. Curr Biol 19:1703–1711. doi:10.1016/j.cub.2009.08.027
Tanenbaum ME, Vale RD, McKenney RJ (2013) Cytoplasmic dynein crosslinks and slides anti-parallel microtubules using its two motor domains. eLife 2:e00943–e00943. doi:10.7554/eLife.00943.020
Tang WY, Gibbons IR (1987) Photosensitized cleavage of dynein heavy chains. Cleavage at the V2 site by irradiation at 365 NM in the presence of oligovanadate. J Biol Chem 262:17728–17734
Théry M, Racine V, Pépin A et al (2005) The extracellular matrix guides the orientation of the cell division axis. Nat Cell Biol 7:947–953. doi:10.1038/ncb1307
Toba S, Watanabe TM, Yamaguchi-Okimoto L et al (2006) Overlapping hand-over-hand mechanism of single molecular motility of cytoplasmic dynein. Proc Natl Acad Sci U S A 103:5741–5745. doi:10.1073/pnas.0508511103
Torisawa T, Nakayama A, Furuta K et al (2011) Functional dissection of LIS1 and NDEL1 towards understanding the molecular mechanisms of cytoplasmic dynein regulation. J Biol Chem 286:1959–1965. doi:10.1074/jbc.M110.169847
Trokter M, Mücke N, Surrey T (2012) Reconstitution of the human cytoplasmic dynein complex. Proc Natl Acad Sci U S A. doi:10.1073/pnas.1210573110
Tsai J-W, Lian W-N, Kemal S et al (2010) Kinesin 3 and cytoplasmic dynein mediate interkinetic nuclear migration in neural stem cells. Nat Neurosci 13:1463–1471. doi:10.1038/nn.2665
Vaisberg EA, Koonce MP, McIntosh JR (1993) Cytoplasmic dynein plays a role in mammalian mitotic spindle formation. J Cell Biol 123:849–858
Vale RD, Reese TS, Sheetz MP (1985) Identification of a novel force-generating protein, kinesin, involved in microtubule-based motility. Cell 42:39–50
van Heesbeen RGHP, Raaijmakers JA, Tanenbaum ME, Medema RH (2013) Nuclear envelope-associated dynein cooperates with Eg5 to drive prophase centrosome separation. Commun Integr Biol 6:e23841. doi:10.4161/cib.23841
Vanneste D, Takagi M, Imamoto N, Vernos I (2009) The role of Hklp2 in the stabilization and maintenance of spindle bipolarity. Curr Biol 19:1712–1717. doi:10.1016/j.cub.2009.09.019
Varma D, Monzo P, Stehman SA, Vallee RB (2008) Direct role of dynein motor in stable kinetochore-microtubule attachment, orientation, and alignment. J Cell Biol 182:1045–1054
Vaughan KT, Vallee RB (1995) Cytoplasmic dynein binds dynactin through a direct interaction between the intermediate chains and p150Glued. J Cell Biol 131:1507–1516
Verde F, Berrez JM, Antony C, Karsenti E (1991) Taxol-induced microtubule asters in mitotic extracts of Xenopus eggs: requirement for phosphorylated factors and cytoplasmic dynein. J Cell Biol 112:1177–1187
Vergnolle MA, Taylor SS (2007) Cenp-F links kinetochores to Ndel1/Nde1/Lis1/dynein microtubule motor complexes. Curr Biol 17:1173–1179
Vleugel M, Hoogendoorn E, Snel B, Kops GJPL (2012) Evolution and function of the mitotic checkpoint. Dev Cell 23:239–250. doi:10.1016/j.devcel.2012.06.013
Vorozhko VV, Emanuele MJ, Kallio MJ et al (2008) Multiple mechanisms of chromosome movement in vertebrate cells mediated through the Ndc80 complex and dynein/dynactin. Chromosoma 117:169–179. doi:10.1007/s00412-007-0135-3
Walczak CE, Verma S, Mitchison TJ (1997) XCTK2: a kinesin-related protein that promotes mitotic spindle assembly in Xenopus laevis egg extracts. J Cell Biol 136:859–870
Walczak CE, Vernos I, Mitchison TJ et al (1998) A model for the proposed roles of different microtubule-based motor proteins in establishing spindle bipolarity. Curr Biol 8:903–913
Wang S, Zheng Y (2011) Identification of a novel dynein binding domain in nudel essential for spindle pole organization in Xenopus egg extract. J Biol Chem 286:587–593. doi:10.1074/jbc.M110.181578
Wang S, Ketcham SA, Schön A et al (2013) Nudel/NudE and Lis1 promote dynein and dynactin interaction in the context of spindle morphogenesis. Mol Biol Cell 24:3522–3533. doi:10.1091/mbc.E13-05-0283
Waterman-Storer CM, Karki S, Holzbaur EL (1995) The p150Glued component of the dynactin complex binds to both microtubules and the actin-related protein centractin (Arp-1). Proc Natl Acad Sci U S A 92:1634–1638
Welburn JP, Grishchuk EL, Backer CB et al (2009) The human kinetochore Ska1 complex facilitates microtubule depolymerization-coupled motility. Dev Cell 16:374–385
Whyte J, Bader JR, Tauhata SBF et al (2008) Phosphorylation regulates targeting of cytoplasmic dynein to kinetochores during mitosis. J Cell Biol 183:819–834. doi:10.1083/jcb.200804114
Williams BC, Karr TL, Montgomery JM, Goldberg ML (1992) The Drosophila l(1)zw10 gene product, required for accurate mitotic chromosome segregation, is redistributed at anaphase onset. J Cell Biol 118:759–773
Woodard GE, Huang NN, Cho H et al (2010) Ric-8A and Gi alpha recruit LGN, NuMA, and dynein to the cell cortex to help orient the mitotic spindle. Mol Cell Biol 30:3519–3530
Wuhr M, Tan ES, Parker SK et al (2010) A model for cleavage plane determination in early amphibian and fish embryos. Curr Biol. doi:10.1016/j.cub.2010.10.024
Xiang X, Osmani AH, Osmani SA et al (1995) NudF, a nuclear migration gene in Aspergillus nidulans, is similar to the human LIS-1 gene required for neuronal migration. Mol Biol Cell 6:297–310
Yagi T (2009) Chapter 1—bioinformatic approaches to dynein heavy chain classification, first edition. Methods Cell Biol Vol 92(92):1–9. doi:10.1016/S0091-679X(08)92001-X
Yamada M, Toba S, Yoshida Y et al (2008) LIS1 and NDEL1 coordinate the plus-end-directed transport of cytoplasmic dynein. EMBO J 27:2471–2483. doi:10.1038/emboj.2008.182
Yang Z, Tulu US, Wadsworth P, Rieder CL (2007) Kinetochore dynein is required for chromosome motion and congression independent of the spindle checkpoint. Curr Biol 17:973–980. doi:10.1016/j.cub.2007.04.056
Yeh E, Skibbens RV, Cheng JW et al (1995) Spindle dynamics and cell cycle regulation of dynein in the budding yeast, Saccharomyces cerevisiae. J Cell Biol 130:687–700
Yeh TY, Quintyne NJ, Scipioni BR et al (2012) Dynactin’s pointed-end complex is a cargo-targeting module. Mol Biol Cell 23:3827–3837. doi:10.1091/mbc.E12-07-0496
Yildiz A, Tomishige M, Vale RD, Selvin PR (2004) Kinesin walks hand-over-hand. Science 303:676–678. doi:10.1126/science.1093753
Zheng Z, Wan Q, Meixiong G, Du Q (2013) Cell cycle-regulated membrane binding of NuMA contributes to efficient anaphase chromosome separation. Mol Biol Cell. doi:10.1091/mbc.E13-08-0474
Zylkiewicz E, Kijanska M, Choi WC et al (2011) The N-terminal coiled-coil of Ndel1 is a regulated scaffold that recruits LIS1 to dynein. J Cell Biol 192:433–445
Acknowledgments
This work was supported by the ZonMW TOP project (40-00812-98-10021) and the NWO Gravitation Program Cancer Genomics.nl to R.H. Medema
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Raaijmakers, J.A., Medema, R.H. Function and regulation of dynein in mitotic chromosome segregation. Chromosoma 123, 407–422 (2014). https://doi.org/10.1007/s00412-014-0468-7
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00412-014-0468-7