A Unique Set of Centrosome Proteins Requires Pericentrin for Spindle-Pole Localization and Spindle Orientation

Chun Ting Chen, Heidi Hehnly, Qing Yu, Debby Farkas, Guoqiang Zheng, Sambra D. Redick, Hui Fang Hung, Rajeev Samtani, Agata Jurczyk, Schahram Akbarian, Carol Wise, Andrew Jackson, Michael Bober, Yin Guo, Cecilia Lo, Stephen Doxsey

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Abstract

Majewski osteodysplastic primordial dwarfism type II (MOPDII) is caused by mutations in the centrosome gene pericentrin (PCNT) that lead to severe pre- and postnatal growth retardation [1]. As in MOPDII patients, disruption of pericentrin (Pcnt) in mice caused a number of abnormalities including microcephaly, aberrant hemodynamics analyzed by in utero echocardiography, and cardiovascular anomalies; the latter being associated with mortality, as in the human condition [1]. To identify the mechanisms underlying these defects, we tested for changes in cell and molecular function. All Pcnt-/- mouse tissues and cells examined showed spindle misorientation. This mouse phenotype was associated with misdirected ventricular septal growth in the heart, decreased proliferative symmetric divisions in brain neural progenitors, and increased misoriented divisions in fibroblasts; the same phenotype was seen in fibroblasts from three MOPDII individuals. Misoriented spindles were associated with disrupted astral microtubules and near complete loss of a unique set of centrosome proteins from spindle poles (ninein, Cep215, centriolin). All these proteins appear to be crucial for microtubule anchoring and all interacted with Pcnt, suggesting that Pcnt serves as a molecular scaffold for this functionally linked set of spindle pole proteins. Importantly, Pcnt disruption had no detectable effect on localization of proteins involved in the cortical polarity pathway (NuMA, p150glued, aPKC). Not only do these data reveal a spindle-pole-localized complex for spindle orientation, but they identify key spindle symmetry proteins involved in the pathogenesis of MOPDII.

Original languageEnglish (US)
Pages (from-to)2327-2334
Number of pages8
JournalCurrent Biology
Volume24
Issue number19
DOIs
StatePublished - Oct 6 2014

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Spindle Poles
centrosomes
Centrosome
dwarfing
Poles
Proteins
proteins
microtubules
fibroblasts
Fibroblasts
mice
Microtubules
phenotype
echocardiography
Phenotype
Echocardiography
hemodynamics
Microcephaly
growth retardation
Hemodynamics

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Chen, C. T., Hehnly, H., Yu, Q., Farkas, D., Zheng, G., Redick, S. D., ... Doxsey, S. (2014). A Unique Set of Centrosome Proteins Requires Pericentrin for Spindle-Pole Localization and Spindle Orientation. Current Biology, 24(19), 2327-2334. https://doi.org/10.1016/j.cub.2014.08.029

A Unique Set of Centrosome Proteins Requires Pericentrin for Spindle-Pole Localization and Spindle Orientation. / Chen, Chun Ting; Hehnly, Heidi; Yu, Qing; Farkas, Debby; Zheng, Guoqiang; Redick, Sambra D.; Hung, Hui Fang; Samtani, Rajeev; Jurczyk, Agata; Akbarian, Schahram; Wise, Carol; Jackson, Andrew; Bober, Michael; Guo, Yin; Lo, Cecilia; Doxsey, Stephen.

In: Current Biology, Vol. 24, No. 19, 06.10.2014, p. 2327-2334.

Research output: Contribution to journalArticle

Chen, CT, Hehnly, H, Yu, Q, Farkas, D, Zheng, G, Redick, SD, Hung, HF, Samtani, R, Jurczyk, A, Akbarian, S, Wise, C, Jackson, A, Bober, M, Guo, Y, Lo, C & Doxsey, S 2014, 'A Unique Set of Centrosome Proteins Requires Pericentrin for Spindle-Pole Localization and Spindle Orientation', Current Biology, vol. 24, no. 19, pp. 2327-2334. https://doi.org/10.1016/j.cub.2014.08.029
Chen, Chun Ting ; Hehnly, Heidi ; Yu, Qing ; Farkas, Debby ; Zheng, Guoqiang ; Redick, Sambra D. ; Hung, Hui Fang ; Samtani, Rajeev ; Jurczyk, Agata ; Akbarian, Schahram ; Wise, Carol ; Jackson, Andrew ; Bober, Michael ; Guo, Yin ; Lo, Cecilia ; Doxsey, Stephen. / A Unique Set of Centrosome Proteins Requires Pericentrin for Spindle-Pole Localization and Spindle Orientation. In: Current Biology. 2014 ; Vol. 24, No. 19. pp. 2327-2334.
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AU - Zheng, Guoqiang

AU - Redick, Sambra D.

AU - Hung, Hui Fang

AU - Samtani, Rajeev

AU - Jurczyk, Agata

AU - Akbarian, Schahram

AU - Wise, Carol

AU - Jackson, Andrew

AU - Bober, Michael

AU - Guo, Yin

AU - Lo, Cecilia

AU - Doxsey, Stephen

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