A kinesin-mediated mechanism that couples centrosomes to nuclei
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Cellular and Molecular Life Sciences
RESEARCH ARTICLE
A kinesin-mediated mechanism that couples centrosomes to nuclei Irina Tikhonenko • Valentin Magidson • Ralph Gra¨f • Alexey Khodjakov • Michael P. Koonce
Received: 16 July 2012 / Revised: 3 October 2012 / Accepted: 22 October 2012 / Published online: 17 November 2012 Ó Springer Basel 2012
Abstract The M-type kinesin isoform, Kif9, has recently been implicated in maintaining a physical connection between the centrosome and nucleus in Dictyostelium discoideum. However, the mechanism by which Kif9 functions to link these two organelles remains obscure. Here we demonstrate that the Kif9 protein is localized to the nuclear envelope and is concentrated in the region underlying the centrosome point of attachment. Nuclear anchorage appears mediated through a specialized transmembrane domain located in the carboxyl terminus. Kif9 interacts with microtubules in in vitro binding assays and effects an endwise depolymerization of the polymer. These results suggest a model whereby Kif9 is anchored to the nucleus and generates a pulling force that reels the centrosome up against the nucleus. This is a novel activity for a kinesin motor, one important for progression of cells into mitosis and to ensure centrosome-nuclear parity in a multinuclear environment. Keywords Centrosome Kinesin Microtubule Dictyostelium
I. Tikhonenko V. Magidson A. Khodjakov M. P. Koonce (&) Division of Translational Medicine, Wadsworth Center, NYS Department of Health, Empire State Plaza, PO Box 509, Albany, NY 12201-0509, USA e-mail: [email protected] R. Gra¨f Department of Cell Biology, Institute for Biochemistry and Biology, University of Potsdam, Karl-Liebknecht-Strasse 24-25, Haus 26, 14476 Potsdam-Golm, Germany
Introduction Interactions between centrosomes and nuclei are well known to play fundamental roles in eukaryotic cell function, particularly during motility and division processes. During interphase, centrosomes nucleate microtubules that connect nuclei to force-generating machinery. These interactions are important because they coordinate nuclear transport, maintain nuclear position during cell movement, and perhaps even couple extracellular signals to nuclear alterations that influence gene expression. Upon entering mitosis, a close association between centrosomes and nuclei facilitates the attachment of spindle microtubules to chromosomes, which is necessary to ensure the accurate segregation of genetic material. Primarily acting through microtubules, genetic and molecular analyses have begun to reveal a complex framework of proteins that interconnect centrosomes and nuclei, including the KASH/SUN families that span the nuclear envelope (NE) and serve to establish linkages with dynein and kinesin motors (reviewed in [1]). Yet despite this work, the full range of molecular connections, particularly in nonvertebrate eukaryotes with structurally diverse centrosome-nuclear relationships remains poorly understood. In vertebrate cells, centrosomes are located in the cytoplas
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