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Cited by 26Microtubule and mitosis dynamicsNuclear Structure and FunctionGenomics and Chromatin Dynamics

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BICD2 phosphorylation regulates dynein function and centrosome separation in G2 and M

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Gallisà-Suñé, Núria, Sànchez-Fernàndez-de-Landa, Paula, Zimmermann, Fabian, Serna, Marina, Regué, Laura, Paz, Joel, Llorca, Oscar, Lüders, Jens, Roig, Joan·2023·Nature Communications
DOI 10.1038/s41467-023-38116-1PMC PMC10140047

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Abstract

The activity of dynein is regulated by a number of adaptors that mediate its interaction with dynactin, effectively activating the motor complex while also connecting it to different cargos. The regulation of adaptors is consequently central to dynein physiology but remains largely unexplored. We now describe that one of the best-known dynein adaptors, BICD2, is effectively activated through phosphorylation. In G2, phosphorylation of BICD2 by CDK1 promotes its interaction with PLK1. In turn, PLK1 phosphorylation of a single residue in the N-terminus of BICD2 results in a structural change that facilitates the interaction with dynein and dynactin, allowing the formation of active motor complexes. Moreover, modified BICD2 preferentially interacts with the nucleoporin RanBP2 once RanBP2 has been phosphorylated by CDK1. BICD2 phosphorylation is central for dynein recruitment to the nuclear envelope, centrosome tethering to the nucleus and centrosome separation in the G2 and M phases of the cell cycle. This work reveals adaptor activation through phosphorylation as crucial for the spatiotemporal regulation of dynein activity.

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  1. Reck-Peterson, S. L., Redwine, W. B., Vale, R. D. & Carter, A. P. The cytoplasmic dynein transport machinery and its many cargoes. Nat. Rev. Mol. Cell Biol. 19, 382–398 (2018). · DOI
  2. Canty, J. T., Tan, R., Kusakci, E., Fernandes, J. & Yildiz, A. Structure and mechanics of dynein motors. Annu. Rev. Biophys. 50, 549–574 (2021). · DOI
  3. Tanenbaum, M. E., Akhmanova, A. & Medema, R. H. Bi-directional transport of the nucleus by dynein and kinesin-1. Commun. Integr. Biol. 4, 21–25 (2011). · DOI
  4. Yadav, S. & Linstedt, A. D. Golgi positioning. Cold Spring Harb. Perspect. Biol. 3, a005322 (2011). · DOI
  5. Agircan, F. G., Schiebel, E. & Mardin, B. R. Separate to operate: control of centrosome positioning and separation. Philos. Trans. R. Soc. Lond. B Biol. Sci. 369, 20130461 (2014). · DOI
  6. Raaijmakers, J. A. & Medema, R. H. Function and regulation of dynein in mitotic chromosome segregation. Chromosoma 123, 407–422 (2014). · DOI
  7. Olenick, M. A. & Holzbaur, E. L. F. Dynein activators and adaptors at a glance. J. Cell Sci. 132, jcs227132 (2019). · DOI
  8. Hoogenraad, C. C. & Akhmanova, A. Bicaudal D family of motor adaptors: linking dynein motility to cargo binding. Trends Cell Biol. 26, 327–340 (2016). · DOI
  9. Hoogenraad, C. C. et al. Bicaudal D induces selective dynein-mediated microtubule minus end-directed transport. EMBO J. 22, 6004–6015 (2003). · DOI
  10. Splinter, D. et al. BICD2, dynactin and LIS1 cooperate in regulating dynein recruitment to cellular structures. Mol. Biol. Cell 23, 4226–4241 (2012). · DOI
  11. Urnavicius, L. et al. The structure of the dynactin complex and its interaction with dynein. Science 347, 1441–1446 (2015). · DOI · Paper page
  12. Lee, I.-G. et al. A conserved interaction of the dynein light intermediate chain with dynein-dynactin effectors necessary for processivity. Nat. Commun. 9, 986 (2018). · DOI
  13. Gama, J. B. et al. Molecular mechanism of dynein recruitment to kinetochores by the Rod-Zw10-Zwilch complex and Spindly. J. Cell Biol. 216, 943–960 (2017). · DOI
  14. Hoogenraad, C. C. et al. Mammalian Golgi-associated Bicaudal-D2 functions in the dynein-dynactin pathway by interacting with these complexes. EMBO J. 20, 4041–4054 (2001). · DOI
  15. McKenney, R. J., Huynh, W., Tanenbaum, M. E., Bhabha, G. & Vale, R. D. Activation of cytoplasmic dynein motility by dynactin-cargo adapter complexes. Science 345, 337–341 (2014). · DOI
  16. Schlager, M. A., Hoang, H. T., Urnavicius, L., Bullock, S. L. & Carter, A. P. In vitro reconstitution of a highly processive recombinant human dynein complex. EMBO J. 33, 1855–1868 (2014). · DOI
  17. Matanis, T. et al. Bicaudal-D regulates COPI-independent Golgi-ER transport by recruiting the dynein-dynactin motor complex. Nat. Cell Biol. 4, 986–992 (2002). · DOI · Paper page
  18. Grigoriev, I. et al. Rab6 regulates transport and targeting of exocytotic carriers. Dev. Cell 13, 305–314 (2007). · DOI · Paper page
  19. Huynh, W. & Vale, R. D. Disease-associated mutations in human BICD2 hyperactivate motility of dynein-dynactin. J. Cell Biol. 216, 3051–3060 (2017). · DOI
  20. Splinter, D. et al. Bicaudal D2, dynein, and kinesin-1 associate with nuclear pore complexes and regulate centrosome and nuclear positioning during mitotic entry. PLoS Biol. 8, e1000350 (2010). · DOI
  21. Baffet, A. D., Hu, D. J. & Vallee, R. B. Cdk1 activates pre-mitotic nuclear envelope dynein recruitment and apical nuclear migration in neural stem cells. Dev. Cell 33, 703–716 (2015). · DOI
  22. Gonçalves, J. C., Quintremil, S., Yi, J. & Vallee, R. B. Nesprin-2 recruitment of BicD2 to the nuclear envelope controls dynein/kinesin-mediated neuronal migration in vivo. Curr. Biol. 30, 3116–3129.e4 (2020). · DOI
  23. Gönczy, P., Pichler, S., Kirkham, M. & Hyman, A. A. 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 (1999). · DOI
  24. Robinson, J. T., Wojcik, E. J., Sanders, M. A., McGrail, M. & Hays, T. S. Cytoplasmic dynein is required for the nuclear attachment and migration of centrosomes during mitosis in Drosophila. J. Cell Biol. 146, 597–608 (1999). · DOI
  25. Sharp, D. J. et al. Functional coordination of three mitotic motors in Drosophila embryos. Mol. Biol. Cell 11, 241–253 (2000). · DOI
  26. Bolhy, S. et al. A Nup133-dependent NPC-anchored network tethers centrosomes to the nuclear envelope in prophase. J. Cell Biol. 192, 855–871 (2011). · DOI
  27. Raaijmakers, J. A. et al. Nuclear envelope-associated dynein drives prophase centrosome separation and enables Eg5-independent bipolar spindle formation. EMBO J. 31, 4179–4190 (2012). · DOI
  28. Salina, D. et al. Cytoplasmic dynein as a facilitator of nuclear envelope breakdown. Cell 108, 97–107 (2002). · DOI
  29. Hu, D. J.-K. et al. Dynein recruitment to nuclear pores activates apical nuclear migration and mitotic entry in brain progenitor cells. Cell 154, 1300–1313 (2013). · DOI
  30. Doobin, D. J., Kemal, S., Dantas, T. J. & Vallee, R. B. Severe NDE1-mediated microcephaly results from neural progenitor cell cycle arrests at multiple specific stages. Nat. Commun. 7, 12551 (2016). · DOI
  31. Bruinsma, W., Raaijmakers, J. A. & Medema, R. H. Switching Polo-like kinase-1 on and off in time and space. Trends Biochem. Sci. 37, 534–542 (2012). · DOI
  32. Zitouni, S., Nabais, C., Jana, S. C., Guerrero, A. & Bettencourt-Dias, M. Polo-like kinases: structural variations lead to multiple functions. Nat. Rev. Mol. Cell Biol. 15, 433–452 (2014). · DOI
  33. Mirouse, V., Formstecher, E. & Couderc, J. L. Interaction between Polo and BicD proteins links oocyte determination and meiosis control in Drosophila. Development 133, 4005–4013 (2006). · DOI
  34. Hutchins, J. R. A. et al. Systematic localization and purification of human protein complexes identifies chromosome segregation proteins. Science 328, 593–599 (2010). · DOI
  35. Redwine, W. B. et al. The human cytoplasmic dynein interactome reveals novel activators of motility. eLife 6, e28257 (2017). · DOI
  36. Elia, A. E. H., Cantley, L. C. & Yaffe, M. B. Proteomic screen finds pSer/pThr-binding domain localizing Plk1 to mitotic substrates. Science 299, 1228–1231 (2003). · DOI
  37. Songyang, Z. et al. Use of an oriented peptide library to determine the optimal substrates of protein kinases. Curr. Biol. 4, 973–982 (1994). · DOI
  38. Nakajima, H., Toyoshima-Morimoto, F., Taniguchi, E. & Nishida, E. Identification of a consensus motif for Plk (Polo-like kinase) phosphorylation reveals Myt1 as a Plk1 substrate. J. Biol. Chem. 278, 25277–25280 (2003). · DOI
  39. Alexander, J. et al. Spatial exclusivity combined with positive and negative selection of phosphorylation motifs is the basis for context-dependent mitotic signaling. Sci. Signal. 4, ra42 (2011). · DOI
  40. Chen, J. V., Buchwalter, R. A., Kao, L.-R. & Megraw, T. L. A splice variant of centrosomin converts mitochondria to microtubule-organizing centers. Curr. Biol. 27, 1928–1940.e6 (2017). · DOI
  41. Noell, C. R. et al. Role of coiled-coil registry shifts in activation of human bicaudal D2 for dynein recruitment upon cargo-binding. J. Phys. Chem. Lett. 10, 4362–4367 (2019). · DOI
  42. Fagiewicz, R. et al. In vitro characterization of the full-length human dynein-1 cargo adaptor BicD2. Structure 30, 1470–1478.e3 (2022). · DOI · Paper page
  43. Vassilev, L. T. et al. Selective small-molecule inhibitor reveals critical mitotic functions of human CDK1. Proc. Natl Acad. Sci. USA 103, 10660–10665 (2006). · DOI
  44. Steegmaier, M. et al. BI 2536, a potent and selective inhibitor of Polo-like Kinase 1, inhibits tumor growth in vivo. Curr. Biol. 17, 316–322 (2007). · DOI
  45. Meijer, L. et al. Biochemical and cellular effects of roscovitine, a potent and selective inhibitor of the cyclin-dependent kinases cdc2, cdk2 and cdk5. Eur. J. Biochem. 243, 527–536 (1997). · DOI · Paper page
  46. Skoufias, D. A. et al. S-trityl-L-cysteine is a reversible, tight binding inhibitor of the human kinesin Eg5 that specifically blocks mitotic progression. J. Biol. Chem. 281, 17559–17569 (2006). · DOI
  47. Tanenbaum, M. E., Macrek, L., Galjart, N. & Medema, R. H. Dynein, Lis1 and CLIP-170 counteract Eg5-dependent centrosome separation during bipolar spindle assembly. EMBO J. 27, 3235–3245 (2008). · DOI
  48. Bertran, M. T. et al. Nek9 is a Plk1-activated kinase that controls early centrosome separation through Nek6/7 and Eg5. EMBO J. 30, 2634–2647 (2011). · DOI
  49. Eibes, S. et al. Nek9 phosphorylation defines a new role for TPX2 in Eg5-dependent centrosome separation before nuclear envelope breakdown. Curr. Biol. 28, 121–129.e4 (2018). · DOI
  50. Terawaki, S.-I. I., Yoshikane, A., Higuchi, Y. & Wakamatsu, K. Structural basis for cargo binding and autoinhibition of Bicaudal-D1 by a parallel coiled-coil with homotypic registry. Biochem. Biophys. Res. Commun. 460, 451–456 (2015). · DOI
  51. Urnavicius, L. et al. Cryo-EM shows how dynactin recruits two dyneins for faster movement. Nature 554, 202–206 (2018). · DOI
  52. Olenick, M. A., Tokito, M., Boczkowska, M., Dominguez, R. & Holzbaur, E. L. F. Hook adaptors induce unidirectional processive motility by enhancing the dynein-dynactin interaction. J. Biol. Chem. 291, 18239–18251 (2016). · DOI
  53. Stuurman, N. et al. Interactions between coiled-coil proteins: Drosophila lamin Dm0 binds to the bicaudal-D protein. Eur. J. Cell Biol. 78, 278–287 (1999). · DOI
  54. Sladewski, T. E. et al. Recruitment of two dyneins to an mRNA-dependent Bicaudal D transport complex. eLife 7, e36306 (2018). · DOI
  55. Wynne, C. L. & Vallee, R. B. Cdk1 phosphorylation of the dynein adapter Nde1 controls cargo binding from G2 to anaphase. J. Cell Biol. 217, 3019–3029 (2018). · DOI
  56. Li, H. et al. Polo-like kinase 1 phosphorylation of p150Glued facilitates nuclear envelope breakdown during prophase. Proc. Natl Acad. Sci. USA 107, 14633–14638 (2010). · DOI
  57. Gibson, J. M. et al. Coil-to-α-helix transition at the Nup358-BicD2 interface activates BicD2 for dynein recruitment. eLife 11, e74714 (2022). · DOI
  58. Schlager, M. A. et al. Pericentrosomal targeting of Rab6 secretory vesicles by Bicaudal-D-related protein 1 (BICDR-1) regulates neuritogenesis. EMBO J. 29, 1637–1651 (2010). · DOI · Paper page
  59. Noell, C. R. et al. A quantitative model for BicD2/cargo interactions. Biochemistry 57, 6538–6550 (2018). · DOI
  60. Raaijmakers, J. A., Tanenbaum, M. E. & Medema, R. H. Systematic dissection of dynein regulators in mitosis. J. Cell Biol. 201, 201–215 (2013). · DOI
  61. Stiff, T. et al. Prophase-specific perinuclear actin coordinates centrosome separation and positioning to ensure accurate chromosome segregation. Cell Rep. 31, 107681 (2020). · DOI
  62. Jean, C., Tollon, Y., Raynaud-Messina, B. & Wright, M. The mammalian interphase centrosome: two independent units maintained together by the dynamics of the microtubule cytoskeleton. Eur. J. Cell Biol. 78, 549–560 (1999). · DOI
  63. Meraldi, P. & Nigg, E. A. Centrosome cohesion is regulated by a balance of kinase and phosphatase activities. J. Cell Sci. 114, 3749–3757 (2001). · DOI
  64. Silkworth, W. T., Nardi, I. K., Paul, R., Mogilner, A. & Cimini, D. Timing of centrosome separation is important for accurate chromosome segregation. Mol. Biol. Cell 23, 401–411 (2012). · DOI
  65. Fumoto, K., Hoogenraad, C. C. & Kikuchi, A. GSK-3beta-regulated interaction of BICD with dynein is involved in microtubule anchorage at centrosome. EMBO J. 25, 5670–5682 (2006). · DOI
  66. Suter, B. & Steward, R. Requirement for phosphorylation and localization of the Bicaudal-D protein in Drosophila oocyte differentiation. Cell 67, 917–926 (1991). · DOI
  67. Dillman, J. F. & Pfister, K. K. Differential phosphorylation in vivo of cytoplasmic dynein associated with anterogradely moving organelles. J. Cell Biol. 127, 1671–1681 (1994). · DOI
  68. Bader, J. R. et al. Polo-like kinase1 is required for recruitment of dynein to kinetochores during mitosis. J. Biol. Chem. 286, 20769–20777 (2011). · DOI
  69. Weissmann, F. & Peters, J.-M. Expressing multi-subunit complexes using biGBac. Methods Mol. Biol. 1764, 329–343 (2018). · DOI
  70. Scholz, J. & Suppmann, S. A new single-step protocol for rapid baculovirus-driven protein production in insect cells. BMC Biotechnol. 17, 83 (2017). · DOI
  71. Roig, J., Mikhailov, A., Belham, C. & Avruch, J. Nercc1, a mammalian NIMA-family kinase, binds the Ran GTPase and regulates mitotic progression. Genes Dev. 16, 1640–1658 (2002). · DOI
  72. Punjani, A., Rubinstein, J. L., Fleet, D. J. & Brubaker, M. A. A. cryoSPARC: algorithms for rapid unsupervised cryo-EM structure determination. Nat. Methods 14, 290–296 (2017). · DOI · Paper page

Metadata

Authors
Gallisà-Suñé, N., Sànchez-Fernàndez-de-Landa, P., Zimmermann, F., Serna, M., Regué, L., Paz, J., Llorca, O., Lüders, J., & Roig, J.
Affiliations
  • Consejo Superior de Investigaciones Científicas (ES)
  • Institute for Research in Biomedicine (ES)
  • Spanish National Cancer Research Centre (ES)
Corresponding author
Roig, Joan
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2023-04-27
Volume
14
Issue
1
Pages
2434-2434
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-023-38116-1
PMC
PMC10140047
OpenAlex
W4367176084
Cited by
26
References
4
Citations by year
2026: 9 · 2025: 10 · 2024: 4 · 2023: 3
FWCI
3.76
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion, cc-by)
  • RePEc: Research Papers in Economics (submittedVersion)
  • Dipòsit Digital de la Universitat de Barcelona (Universitat de Barcelona) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Ministry of Economy and Competitiveness | Agencia Estatal de Investigación (BFU2014-58422-P, PGC2018-096307-B-I00, PID2021-127045NB-I00))
  • Generalitat de Catalunya (SGR 1089)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Keywords
BICD2, dynein, dynactin, phosphorylation, CDK1, PLK1, RanBP2, centrosome separation, nuclear envelope, G2/M phase
MeSH terms
Dynactin Complex, Cell Cycle, Dyneins, Microtubule-Associated Proteins, Phosphorylation, Centrosome

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