Cep192 controls the balance of centrosome and non-centrosomal microtubules during interphase

Brian P. O'Rourke, Maria Ana Gomez-Ferreria, Robin H. Berk, Alexandra M U Hackl, Matthew P. Nicholas, Sean C. O'Rourke, Laurence Pelletier, David J. Sharp

Research output: Contribution to journalArticle

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Abstract

Cep192 is a centrosomal protein that contributes to the formation and function of the mitotic spindle in mammalian cells. Cep192's mitotic activities stem largely from its role in the recruitment to the centrosome of numerous additional proteins such as gamma-tubulin and Pericentrin. Here, we examine Cep192's function in interphase cells. Our data indicate that, as in mitosis, Cep192 stimulates the nucleation of centrosomal microtubules thereby regulating the morphology of interphase microtubule arrays. Interestingly, however, cells lacking Cep192 remain capable of generating normal levels of MTs as the loss of centrosomal microtubules is augmented by MT nucleation from other sites, most notably the Golgi apparatus. The depletion of Cep192 results in a significant decrease in the level of centrosome-associated gamma-tubulin, likely explaining its impact on centrosome microtubule nucleation. However, in stark contrast to mitosis, Cep192 appears to maintain an antagonistic relationship with Pericentrin at interphase centrosomes. Interphase cells depleted of Cep192 display significantly higher levels of centrosome-associated Pericentrin while overexpression of Cep192 reduces the levels of centrosomal Pericentrin. Conversely, depletion of Pericentrin results in elevated levels of centrosomal Cep192 and enhances microtubule nucleation at centrosomes, at least during interphase. Finally, we show that depletion of Cep192 negatively impacts cell motility and alters normal cell polarization. Our current working hypothesis is that the microtubule nucleating capacity of the interphase centrosome is determined by an antagonistic balance of Cep192, which promotes nucleation, and Pericentrin, which inhibits nucleation. This in turn determines the relative abundance of centrosomal and noncentrosomal microtubules that tune cell movement and shape.

Original languageEnglish (US)
Article numbere101001
JournalPLoS One
Volume9
Issue number6
DOIs
StatePublished - Jun 27 2014

Fingerprint

centrosomes
Centrosome
Interphase
Microtubules
interphase
microtubules
Nucleation
Tubulin
tubulin
cell movement
Mitosis
mitosis
Cell Movement
cells
Cells
mitotic spindle apparatus
Spindle Apparatus
Cell Shape
Golgi Apparatus
Golgi apparatus

ASJC Scopus subject areas

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

Cite this

O'Rourke, B. P., Gomez-Ferreria, M. A., Berk, R. H., Hackl, A. M. U., Nicholas, M. P., O'Rourke, S. C., ... Sharp, D. J. (2014). Cep192 controls the balance of centrosome and non-centrosomal microtubules during interphase. PLoS One, 9(6), [e101001]. https://doi.org/10.1371/journal.pone.0101001

Cep192 controls the balance of centrosome and non-centrosomal microtubules during interphase. / O'Rourke, Brian P.; Gomez-Ferreria, Maria Ana; Berk, Robin H.; Hackl, Alexandra M U; Nicholas, Matthew P.; O'Rourke, Sean C.; Pelletier, Laurence; Sharp, David J.

In: PLoS One, Vol. 9, No. 6, e101001, 27.06.2014.

Research output: Contribution to journalArticle

O'Rourke, BP, Gomez-Ferreria, MA, Berk, RH, Hackl, AMU, Nicholas, MP, O'Rourke, SC, Pelletier, L & Sharp, DJ 2014, 'Cep192 controls the balance of centrosome and non-centrosomal microtubules during interphase', PLoS One, vol. 9, no. 6, e101001. https://doi.org/10.1371/journal.pone.0101001
O'Rourke BP, Gomez-Ferreria MA, Berk RH, Hackl AMU, Nicholas MP, O'Rourke SC et al. Cep192 controls the balance of centrosome and non-centrosomal microtubules during interphase. PLoS One. 2014 Jun 27;9(6). e101001. https://doi.org/10.1371/journal.pone.0101001
O'Rourke, Brian P. ; Gomez-Ferreria, Maria Ana ; Berk, Robin H. ; Hackl, Alexandra M U ; Nicholas, Matthew P. ; O'Rourke, Sean C. ; Pelletier, Laurence ; Sharp, David J. / Cep192 controls the balance of centrosome and non-centrosomal microtubules during interphase. In: PLoS One. 2014 ; Vol. 9, No. 6.
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AB - Cep192 is a centrosomal protein that contributes to the formation and function of the mitotic spindle in mammalian cells. Cep192's mitotic activities stem largely from its role in the recruitment to the centrosome of numerous additional proteins such as gamma-tubulin and Pericentrin. Here, we examine Cep192's function in interphase cells. Our data indicate that, as in mitosis, Cep192 stimulates the nucleation of centrosomal microtubules thereby regulating the morphology of interphase microtubule arrays. Interestingly, however, cells lacking Cep192 remain capable of generating normal levels of MTs as the loss of centrosomal microtubules is augmented by MT nucleation from other sites, most notably the Golgi apparatus. The depletion of Cep192 results in a significant decrease in the level of centrosome-associated gamma-tubulin, likely explaining its impact on centrosome microtubule nucleation. However, in stark contrast to mitosis, Cep192 appears to maintain an antagonistic relationship with Pericentrin at interphase centrosomes. Interphase cells depleted of Cep192 display significantly higher levels of centrosome-associated Pericentrin while overexpression of Cep192 reduces the levels of centrosomal Pericentrin. Conversely, depletion of Pericentrin results in elevated levels of centrosomal Cep192 and enhances microtubule nucleation at centrosomes, at least during interphase. Finally, we show that depletion of Cep192 negatively impacts cell motility and alters normal cell polarization. Our current working hypothesis is that the microtubule nucleating capacity of the interphase centrosome is determined by an antagonistic balance of Cep192, which promotes nucleation, and Pericentrin, which inhibits nucleation. This in turn determines the relative abundance of centrosomal and noncentrosomal microtubules that tune cell movement and shape.

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