TY - JOUR
T1 - Human Cep192 Is Required for Mitotic Centrosome and Spindle Assembly
AU - Gomez-Ferreria, Maria Ana
AU - Rath, Uttama
AU - Buster, Daniel W.
AU - Chanda, Sumit K.
AU - Caldwell, Jeremy S.
AU - Rines, Daniel R.
AU - Sharp, David J.
N1 - Funding Information:
We thank J.L. Salisbury (Mayo Clinic Foundation) for the centrin antibody and the HeLa cells expressing GFP-centrin-2 and F.J. McNally (University of California) for the katanin p60 antibody. We are also grateful to L. Haren and A. Merdes (CNRS, Toulouse, France) for the antibodies against NEDD1, GCP-2, and GCP-4. This work was supported by grants from National Institutes of Health to D.J.S., and in part by Philip Morris USA, Inc. D.J.S. is a Scholar of the Leukemia and Lymphoma Society. M.A.G.F. is supported by a fellowship from the Spanish Ministry of Education and Science.
PY - 2007/11/20
Y1 - 2007/11/20
N2 - 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 γ-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 γ-tubulin, pericentrin, or other pericentriolar proteins into an organized PCM. Alternatively, overexpression of Cep192 results in the formation of multiple, extracentriolar foci of γ-tubulin and pericentrin. Together, our findings support the hypothesis that Cep192 stimulates the formation of the scaffolding upon which γ-tubulin ring complexes and other proteins involved in microtubule nucleation and spindle assembly become functional during mitosis.
AB - 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 γ-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 γ-tubulin, pericentrin, or other pericentriolar proteins into an organized PCM. Alternatively, overexpression of Cep192 results in the formation of multiple, extracentriolar foci of γ-tubulin and pericentrin. Together, our findings support the hypothesis that Cep192 stimulates the formation of the scaffolding upon which γ-tubulin ring complexes and other proteins involved in microtubule nucleation and spindle assembly become functional during mitosis.
KW - CELLCYCLE
UR - http://www.scopus.com/inward/record.url?scp=36049016731&partnerID=8YFLogxK
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U2 - 10.1016/j.cub.2007.10.019
DO - 10.1016/j.cub.2007.10.019
M3 - Article
C2 - 17980596
AN - SCOPUS:36049016731
SN - 0960-9822
VL - 17
SP - 1960
EP - 1966
JO - Current Biology
JF - Current Biology
IS - 22
ER -