Abstract
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.
MeSH Terms
Binding Sites/genetics
Cell Cycle Proteins/genetics,metabolism,physiology
Cell Line, Tumor
Cytokinesis/physiology
Cytoplasm/metabolism
HeLa Cells
Humans
Intracellular Signaling Peptides and Proteins
Kinesins/genetics,metabolism,physiology
Microtubule-Associated Proteins/metabolism
Models, Genetic
Oncogene Proteins/genetics,metabolism,physiology
Protein Binding
Protein Serine-Threonine Kinases/genetics,metabolism,physiology
RNA, Small Interfering/genetics
Spindle Apparatus/metabolism
Transfection
Chemicals
Cell Cycle Proteins
Intracellular Signaling Peptides and Proteins
KIF23 protein, human
Microtubule-Associated Proteins
Oncogene Proteins
PRC1 protein, human
RNA, Small Interfering
citron-kinase
Protein Serine-Threonine Kinases
KIF14 protein, human
Kinesins
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Gruneberg Ulrike
Department of Cell Biology, Max-Planck-Institute of Biochemistry, 82152 Martinsried, Germany.
Neef Rüdiger
Li Xiuling
Chan Eunice H Y
Chalamalasetty Ravindra B
Nigg Erich A
Barr Francis A
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