Bimodal Binding of STIL to Plk4 Controls Proper Centriole Copy Number

Cell Rep. 2018 Jun 12;23(11):3160-3169.e4. doi: 10.1016/j.celrep.2018.05.030.

Abstract

The number of centrioles is tightly controlled to ensure bipolar spindle assembly, which is a prerequisite to maintain genome integrity. However, our understanding of the fundamental principle that governs the formation of a single procentriole per parental centriole is incomplete. Here, we show that the local restriction of Plk4, a master regulator of the procentriole formation, is achieved by a bimodal interaction of STIL with Plk4. We demonstrate that the conserved short coiled-coil region of STIL binds to and protects Plk4 from protein degradation at the site of procentriole formation. On the other hand, the conserved C-terminal region of STIL named truncated in microcephaly (TIM) domain promotes autophosphorylation and degradation of adjacent Plk4 by the direct interaction. Thus, we propose that positive and negative regulation based on the bimodal binding of Plk4 and STIL ensures the formation of a single procentriole per parental centriole.

Keywords: Plk4; STIL; cell division; centriole duplication; centrosome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Amino Acid Motifs
  • Animals
  • Cell Line
  • Centrioles / metabolism*
  • HEK293 Cells
  • Humans
  • Intracellular Signaling Peptides and Proteins / antagonists & inhibitors
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Phosphorylation
  • Protein Binding
  • Protein Domains
  • Protein Serine-Threonine Kinases / antagonists & inhibitors
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism*
  • RNA Interference
  • RNA, Small Interfering / metabolism
  • Sequence Alignment

Substances

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