Direct interaction of Plk4 with STIL ensures formation of a single procentriole per parental centriole

Nat Commun. 2014 Oct 24;5:5267. doi: 10.1038/ncomms6267.

Abstract

Formation of one procentriole next to each pre-existing centriole is essential for centrosome duplication, robust bipolar spindle assembly and maintenance of genome integrity. However, the mechanisms maintaining strict control over centriole copy number are incompletely understood. Here we show that Plk4 and STIL, the key regulators of centriole formation, form a protein complex that provides a scaffold for recruiting HsSAS-6, a major component of the centriolar cartwheel, at the onset of procentriole formation. Furthermore, we demonstrate that phosphorylation of STIL by Plk4 facilitates the STIL/HsSAS-6 interaction and centriolar loading of HsSAS-6. We also provide evidence that negative feedback by centriolar STIL regulates bimodal centriolar distribution of Plk4 and seemingly restricts occurrence of procentriole formation to one site on each parental centriole. Overall, these findings suggest a mechanism whereby coordinated action of three critical factors ensures formation of a single procentriole per parental centriole.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / genetics
  • Amino Acid Motifs
  • Amino Acid Sequence
  • Animals
  • Cell Cycle
  • Cell Cycle Proteins / metabolism
  • Cell Line
  • Centrioles / metabolism*
  • HEK293 Cells
  • Humans
  • Immunoprecipitation
  • Intracellular Signaling Peptides and Proteins / chemistry
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Models, Biological
  • Molecular Sequence Data
  • Phosphorylation
  • Protein Binding
  • Protein-Serine-Threonine Kinases / metabolism*
  • RNA, Small Interfering / metabolism
  • Sequence Alignment

Substances

  • 3' Untranslated Regions
  • Cell Cycle Proteins
  • Intracellular Signaling Peptides and Proteins
  • RNA, Small Interfering
  • SASS6 protein, human
  • STIL protein, human
  • PLK4 protein, human
  • Protein-Serine-Threonine Kinases