Casein kinase 1 family proteins promote Slimb-dependent Expanded degradation

Elife. 2019 Sep 30;8:e46592. doi: 10.7554/eLife.46592.

Abstract

Hippo signalling integrates diverse stimuli related to epithelial architecture to regulate tissue growth and cell fate decisions. The Hippo kinase cascade represses the growth-promoting transcription co-activator Yorkie. The FERM protein Expanded is one of the main upstream Hippo signalling regulators in Drosophila as it promotes Hippo kinase signalling and directly inhibits Yorkie. To fulfil its function, Expanded is recruited to the plasma membrane by the polarity protein Crumbs. However, Crumbs-mediated recruitment also promotes Expanded turnover via a phosphodegron-mediated interaction with a Slimb/β-TrCP SCF E3 ligase complex. Here, we show that the Casein Kinase 1 (CKI) family is required for Expanded phosphorylation. CKI expression promotes Expanded phosphorylation and interaction with Slimb/β-TrCP. Conversely, CKI depletion in S2 cells impairs Expanded degradation downstream of Crumbs. In wing imaginal discs, CKI loss leads to elevated Expanded and Crumbs levels. Thus, phospho-dependent Expanded turnover ensures a tight coupling of Hippo pathway activity to epithelial architecture.

Keywords: D. melanogaster; casein kinase 1; cell biology; developmental biology; expanded; hippo signalling; tissue growth.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Casein Kinase I / metabolism*
  • Cell Cycle Proteins / metabolism*
  • Drosophila
  • Drosophila Proteins / metabolism*
  • Gene Expression Regulation
  • Membrane Proteins / metabolism*
  • Phosphorylation
  • Protein Binding
  • Protein Interaction Maps
  • Protein Processing, Post-Translational
  • Proteolysis
  • Ubiquitin-Protein Ligases / metabolism*
  • beta-Transducin Repeat-Containing Proteins / metabolism

Substances

  • Cell Cycle Proteins
  • Drosophila Proteins
  • Membrane Proteins
  • beta-Transducin Repeat-Containing Proteins
  • crb protein, Drosophila
  • ex protein, Drosophila
  • slmb protein, Drosophila
  • Ubiquitin-Protein Ligases
  • Casein Kinase I