4.4 Article

PPP1R35 ensures centriole homeostasis by promoting centriole-to-centrosome conversion

Journal

MOLECULAR BIOLOGY OF THE CELL
Volume 29, Issue 23, Pages 2801-2808

Publisher

AMER SOC CELL BIOLOGY
DOI: 10.1091/mbc.E18-08-0525

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Funding

  1. National Institutes of Health [GM-088253]
  2. American Cancer Society [RSG-14-153-01-CCG]
  3. Geoffrey Beene Cancer Research Center
  4. Functional Genomics initiative

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Centriole-to-centrosome conversion (CCC) safeguards centriole homeostasis by coupling centriole duplication with segregation, and is essential for stabilization of mature vertebrate centrioles naturally devoid of the geometric scaffold or the cartwheel. Here we identified PPP1R35, a putative regulator of the protein phosphatase PP1, as a novel centriolar protein required for CCC. We found that PPP1R35 is enriched at newborn daughter centrioles in S or G2 phase. In the absence of PPP1R35, centriole assembly initiates normally in S phase, but none of the nascent centrioles can form active centrosomes or recruit CEP295, an essential factor for CCC. Instead, all PPP1R35-null centrioles, although stable during their birth in interphase, become disintegrated after mitosis upon cartwheel removal. Surprisingly, we found that neither the centriolar localization nor the function of PPP1R35 in CCC requires the putative PP1-interacting motif. PPP1R35 is thus acting upstream of CEP295 to induce CCC for proper centriole maintenance.

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