KIF14 and citron kinase act together to promote efficient cytokinesis

Multiple mitotic kinesins and microtubule-associated proteins (MAPs) act in concert to direct cytokinesis (Glotzer, M. 2005. Science. 307:1735–1739). In anaphase cells, many of these proteins associate with an antiparallel array of microtubules termed the central spindle. The MAP and microtubule-bundling protein PRC1 (protein-regulating cytokinesis 1) is one of the key molecules required for the integrity of this structure (Jiang, W., G. Jimenez, N.J. Wells, T.J. Hope, G.M. Wahl, T. Hunter, and R. Fukunaga. 1998. Mol. Cell. 2:877–885; Mollinari, C., J.P. Kleman, W. Jiang, G. Schoehn, T. Hunter, and R.L. Margolis. 2002. J. Cell Biol. 157:1175–1186). In this study, we identify an interaction between endogenous PRC1 and the previously uncharacterized kinesin KIF14 as well as other mitotic kinesins (MKlp1/CHO1, MKlp2, and KIF4) with known functions in cytokinesis (Hill, E., M. Clarke, and F.A. Barr. 2000. EMBO J. 19:5711–5719; Matuliene, J., and R. Kuriyama. 2002. Mol. Biol. Cell. 13:1832–1845; Kurasawa, Y., W.C. Earnshaw, Y. Mochizuki, N. Dohmae, and K. Todokoro. 2004. EMBO J. 23:3237–3248). We find that KIF14 targets to the central spindle via its interaction with PRC1 and has an essential function in cytokinesis. In KIF14-depleted cells, citron kinase but not other components of the central spindle and cleavage furrow fail to localize. Furthermore, the localization of KIF14 and citron kinase to the central spindle and midbody is codependent, and they form a complex depending on the activation state of citron kinase. Contrary to a previous study (Di Cunto, F., S. Imarisio, E. Hirsch, V. Broccoli, A. Bulfone, A. Migheli, C. Atzori, E. Turco, R. Triolo, G.P. Dotto, et al. 2000. Neuron. 28:115–127), we find a general requirement for citron kinase in human cell division. Together, these findings identify a novel pathway required for efficient cytokinesis.

[1]  T. Misteli,et al.  Human chromokinesin KIF4A functions in chromosome condensation and segregation , 2004, The Journal of cell biology.

[2]  J. Pines,et al.  Four-dimensional control of the cell cycle , 1999, Nature Cell Biology.

[3]  J Hardin,et al.  Cytokinesis and midzone microtubule organization in Caenorhabditis elegans require the kinesin-like protein ZEN-4. , 1998, Molecular biology of the cell.

[4]  S. Narumiya,et al.  Citron kinase, a Rho-dependent kinase, induces di-phosphorylation of regulatory light chain of myosin II. , 2003, Molecular biology of the cell.

[5]  T. Tuschl,et al.  Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells , 2001, Nature.

[6]  E. Nigg,et al.  Relocation of Aurora B from centromeres to the central spindle at the metaphase to anaphase transition requires MKlp2 , 2004, The Journal of cell biology.

[7]  T. Miki,et al.  Human Ect2 Is an Exchange Factor for Rho Gtpases, Phosphorylated in G2/M Phases, and Involved in Cytokinesis , 1999, The Journal of cell biology.

[8]  F. Di Cunto,et al.  Drosophila citron kinase is required for the final steps of cytokinesis. , 2004, Molecular biology of the cell.

[9]  J. Matulienė,et al.  Role of the midbody matrix in cytokinesis: RNAi and genetic rescue analysis of the mammalian motor protein CHO1. , 2004, Molecular biology of the cell.

[10]  S. Eom,et al.  An intramolecular interaction between the FHA domain and a coiled coil negatively regulates the kinesin motor KIF1A , 2004, The EMBO journal.

[11]  D. Glover,et al.  Mutations in sticky lead to defective organization of the contractile ring during cytokinesis and are enhanced by Rho and suppressed by Rac , 2004, The Journal of cell biology.

[12]  E. Nigg,et al.  Phosphorylation of mitotic kinesin-like protein 2 by polo-like kinase 1 is required for cytokinesis , 2003, The Journal of cell biology.

[13]  G. Wahl,et al.  PRC1: a human mitotic spindle-associated CDK substrate protein required for cytokinesis. , 1998, Molecular cell.

[14]  F. Matsumura.  Regulation of myosin II during cytokinesis in higher eukaryotes. , 2005, Trends in cell biology.

[15]  W. Earnshaw,et al.  Essential roles of KIF4 and its binding partner PRC1 in organized central spindle midzone formation , 2004, The EMBO journal.

[16]  F. Di Cunto,et al.  Citron Rho-interacting Kinase, a Novel Tissue-specific Ser/Thr Kinase Encompassing the Rho-Rac-binding Protein Citron* , 1998, The Journal of Biological Chemistry.

[17]  R. Saint,et al.  A RhoGEF and Rho family GTPase-activating protein complex links the contractile ring to cortical microtubules at the onset of cytokinesis. , 2003, Developmental cell.

[18]  Marina Bibikova,et al.  Functional analysis of human microtubule-based motor proteins, the kinesins and dyneins, in mitosis/cytokinesis using RNA interference. , 2005, Molecular biology of the cell.

[19]  R. Saint,et al.  Citron Kinase is an essential effector of the Pbl-activated Rho signalling pathway in Drosophila melanogaster , 2004, Development.

[20]  K. Fujisawa,et al.  Role of citron kinase as a target of the small GTPase Rho in cytokinesis , 1998, Nature.

[21]  Nobutaka Hirokawa,et al.  Analysis of the kinesin superfamily: insights into structure and function. , 2005, Trends in cell biology.

[22]  S. Narumiya,et al.  Citron, a Rho target that affects contractility during cytokinesis , 2000, Microscopy research and technique.

[23]  D. Rose,et al.  A nematode kinesin required for cleavage furrow advancement , 1998, Current Biology.

[24]  F. Barr,et al.  The Rab6‐binding kinesin, Rab6‐KIFL, is required for cytokinesis , 2000, The EMBO journal.

[25]  L. Silengo,et al.  Defective Neurogenesis in Citron Kinase Knockout Mice by Altered Cytokinesis and Massive Apoptosis , 2000, Neuron.

[26]  S. V. Van Doren,et al.  The FHA domain mediates phosphoprotein interactions. , 2000, Journal of cell science.

[27]  H. Bellen,et al.  pavarotti encodes a kinesin-like protein required to organize the central spindle and contractile ring for cytokinesis. , 1998, Genes & development.

[28]  Timothy W Corson,et al.  KIF14 is a candidate oncogene in the 1q minimal region of genomic gain in multiple cancers , 2005, Oncogene.

[29]  S. Narumiya,et al.  Ect2 and MgcRacGAP regulate the activation and function of Cdc42 in mitosis , 2005, The Journal of cell biology.

[30]  M. Glotzer,et al.  An ECT2–centralspindlin complex regulates the localization and function of RhoA , 2005, The Journal of cell biology.

[31]  T. Hunter,et al.  PRC1 is a microtubule binding and bundling protein essential to maintain the mitotic spindle midzone , 2002, The Journal of cell biology.

[32]  Erich A. Nigg,et al.  Cell division: Mitotic kinases as regulators of cell division and its checkpoints , 2001, Nature Reviews Molecular Cell Biology.

[33]  E. Nigg,et al.  Exploring the functional interactions between Aurora B, INCENP, and survivin in mitosis. , 2003, Molecular biology of the cell.

[34]  D. N. Perkins,et al.  Probability‐based protein identification by searching sequence databases using mass spectrometry data , 1999, Electrophoresis.

[35]  M. Glotzer,et al.  Central spindle assembly and cytokinesis require a kinesin-like protein/RhoGAP complex with microtubule bundling activity. , 2002, Developmental cell.

[36]  I. Kiss,et al.  Mutation of a gene for a Drosophila kinesin-like protein, Klp38B, leads to failure of cytokinesis. , 1997, Journal of cell science.

[37]  M. Glotzer,et al.  The Molecular Requirements for Cytokinesis , 2005, Science.

[38]  J. Matulienė,et al.  Kinesin-like protein CHO1 is required for the formation of midbody matrix and the completion of cytokinesis in mammalian cells. , 2002, Molecular biology of the cell.

[39]  P. O’Farrell,et al.  Terminal Cytokinesis Events Uncovered after an RNAi Screen , 2004, Current Biology.

[40]  Russell L. Malmberg,et al.  A standardized kinesin nomenclature , 2004, The Journal of cell biology.