title: Promotion and Suppression of Centriole Duplication Are Catalytically Coupled through PLK4 to Ensure Centriole Homeostasis.
abstract: PLK4 is the major kinase driving centriole duplication. Duplication occurs only once per cell cycle, forming one new (or daughter) centriole that is tightly engaged to the preexisting (or mother) centriole. Centriole engagement is known to block the reduplication of mother centrioles, but the molecular identity responsible for the block remains unclear. Here, we show that the centriolar cartwheel, the geometric scaffold for centriole assembly, forms the identity of daughter centrioles essential for the block, ceasing further duplication of the mother centriole to which it is engaged. To ensure a steady block, we found that the cartwheel requires constant maintenance by PLK4 through phosphorylation of the same substrate that drives centriole assembly, revealing a parsimonious control in which "assembly" and "block for new assembly" are linked through the same catalytic reaction to achieve homeostasis. Our results support a recently deduced model that the cartwheel-bound PLK4 directly suppresses centriole reduplication.
authors.affiliation: Cell Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA; Weill Cornell Graduate School of Medical Sciences, Cornell University, New York, NY 10065, USA.
authors.forename: Minhee
authors.initials: M
authors.lastname: Kim
authors.affiliation: Cell Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Brian P
authors.initials: BP
authors.lastname: O'Rourke
authors.affiliation: Microchemistry and Proteomics Core Facility, Memorial Sloan-Kettering Cancer Center, New York, NY 10065 USA.
authors.forename: Rajesh Kumar
authors.initials: RK
authors.lastname: Soni
authors.affiliation: Molecular Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Prasad V
authors.initials: PV
authors.lastname: Jallepalli
authors.affiliation: Microchemistry and Proteomics Core Facility, Memorial Sloan-Kettering Cancer Center, New York, NY 10065 USA.
authors.forename: Ronald C
authors.initials: RC
authors.lastname: Hendrickson
authors.affiliation: Cell Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA; Weill Cornell Graduate School of Medical Sciences, Cornell University, New York, NY 10065, USA. Electronic address: tsoum@mskcc.org.
authors.forename: Meng-Fu Bryan
authors.initials: MB
authors.lastname: Tsou
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000502:physiology; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002502:Centrioles / Q000378:metabolism* / Q000502:physiology*; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D010766:Phosphorylation / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D017346:Protein Serine-Threonine Kinases