title: SPD-2/CEP192 and CDK Are Limiting for Microtubule-Organizing Center Function at the Centrosome.
abstract: The centrosome acts as the microtubule-organizing center (MTOC) during mitosis in animal cells. Microtubules are nucleated and anchored by γ-tubulin ring complexes (γ-TuRCs) embedded within the centrosome's pericentriolar material (PCM). The PCM is required for the localization of γ-TuRCs, and both are steadily recruited to the centrosome, culminating in a peak in MTOC function in metaphase. In differentiated cells, the centrosome is often attenuated as an MTOC and MTOC function is reassigned to non-centrosomal sites such as the apical membrane in epithelial cells, the nuclear envelope in skeletal muscle, and down the lengths of axons and dendrites in neurons. Hyperactive MTOC function at the centrosome is associated with epithelial cancers and with invasive behavior in tumor cells. Little is known about the mechanisms that limit MTOC activation at the centrosome. Here, we find that MTOC function at the centrosome is completely inactivated during cell differentiation in C. elegans embryonic intestinal cells and MTOC function is reassigned to the apical membrane. In cells that divide after differentiation, the cellular MTOC state switches between the membrane and the centrosome. Using cell fusion experiments in live embryos, we find that the centrosome MTOC state is dominant and that the inactive MTOC state of the centrosome is malleable; fusion of a mitotic cell to a differentiated or interphase cell results in rapid reactivation of the centrosome MTOC. We show that conversion of MTOC state involves the conserved centrosome protein SPD-2/CEP192 and CDK activity from the mitotic cell.
authors.affiliation: Department of Biology, Stanford University, Stanford, CA 94305, USA.
authors.forename: Renzhi
authors.initials: R
authors.lastname: Yang
authors.affiliation: Department of Biology, Stanford University, Stanford, CA 94305, USA. Electronic address: feldmanj@stanford.edu.
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Feldman
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000196:embryology / Q000235:genetics / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism; D002454:Cell Differentiation; D018385:Centrosome / Q000378:metabolism*; D051357:Cyclin-Dependent Kinase 2 / Q000235:genetics* / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000196:embryology / Q000502:physiology; D007422:Intestines / Q000502:physiology; D022101:Microtubule-Organizing Center / Q000378:metabolism*
chemical_list: D029742:Caenorhabditis elegans Proteins; C486131:SPD-2 protein, C elegans; D051357:Cyclin-Dependent Kinase 2