C-terminal-mediated homodimerization of Expanded is critical for its ability to promote Hippo signalling in Drosophila

FEBS Lett. 2022 Jul;596(13):1628-1638. doi: 10.1002/1873-3468.14332. Epub 2022 Mar 17.

Abstract

Hippo signalling plays key role in tissue growth and homeostasis, and its dysregulation is implicated in various human diseases. Expanded (Ex) is an important upstream activator of Hippo signalling; however, how Ex activates Hippo signalling is still poorly understood. Here, we demonstrate that Ex forms a homodimer via C-terminal interaction, and that the ExC2 region (912-1164 aa) is sufficient and essential for Ex dimerization. Functional analysis shows that ExC2 is required for Ex to promote the phosphorylation and inactivation of Yki in Drosophila cells. Further in vivo analysis shows that ExC2 is important for Ex to control Drosophila tissue growth. Our study, thus, uncovers a novel mechanism whereby Ex homodimerization mediates its full activation to promote Hippo signalling in growth control.

Keywords: dimerization; expanded; hippo signaling; tissue growth.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dimerization
  • Drosophila Proteins* / genetics
  • Drosophila Proteins* / metabolism
  • Drosophila melanogaster / metabolism
  • Drosophila* / metabolism
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics
  • Protein Serine-Threonine Kinases / genetics
  • Signal Transduction

Substances

  • Drosophila Proteins
  • Intracellular Signaling Peptides and Proteins
  • Protein Serine-Threonine Kinases