title: Human Cep192 is required for mitotic centrosome and spindle assembly.
abstract: As cells enter mitosis, centrosomes dramatically increase in size and ability to nucleate microtubules. This process, termed centrosome maturation, is driven by the accumulation and activation of gamma-tubulin and other proteins that form the pericentriolar material on centrosomes during G2/prophase. Here, we show that the human centrosomal protein, Cep192 (centrosomal protein of 192 kDa), is an essential component of the maturation machinery. Specifically, we have found that siRNA depletion of Cep192 results in a complete loss of functional centrosomes in mitotic but not interphase cells. In mitotic cells lacking Cep192, microtubules become organized around chromosomes but rarely acquire stable bipolar configurations. These cells contain normal numbers of centrioles but cannot assemble gamma-tubulin, pericentrin, or other pericentriolar proteins into an organized PCM. Alternatively, overexpression of Cep192 results in the formation of multiple, extracentriolar foci of gamma-tubulin and pericentrin. Together, our findings support the hypothesis that Cep192 stimulates the formation of the scaffolding upon which gamma-tubulin ring complexes and other proteins involved in microtubule nucleation and spindle assembly become functional during mitosis.
authors.affiliation: Department of Physiology and Biophysics, Albert Einstein College of Medicine, New York, New York 10461, USA.
authors.forename: Maria Ana
authors.initials: MA
authors.lastname: Gomez-Ferreria
authors.forename: Uttama
authors.initials: U
authors.lastname: Rath
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Buster
authors.forename: Sumit K
authors.initials: SK
authors.lastname: Chanda
authors.forename: Jeremy S
authors.initials: JS
authors.lastname: Caldwell
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Rines
authors.forename: David J
authors.initials: DJ
authors.lastname: Sharp
mesh_terms: D002454:Cell Differentiation / Q000502:physiology; D018385:Centrosome / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D008868:Microtubule Proteins / Q000502:physiology*; D008870:Microtubules / Q000378:metabolism; D008938:Mitosis / Q000502:physiology*; D008941:Spindle Apparatus / Q000378:metabolism*; D014404:Tubulin / Q000502:physiology
chemical_list: C526596:Cep192 protein, human; D002868:Chromosomal Proteins, Non-Histone; D008868:Microtubule Proteins; D014404:Tubulin