The ZO-1 protein Polychaetoid as an upstream regulator of the Hippo pathway in Drosophila

PLoS Genet. 2021 Nov 8;17(11):e1009894. doi: 10.1371/journal.pgen.1009894. eCollection 2021 Nov.

Abstract

The generation of a diversity of photoreceptor (PR) subtypes with different spectral sensitivities is essential for color vision in animals. In the Drosophila eye, the Hippo pathway has been implicated in blue- and green-sensitive PR subtype fate specification. Specifically, Hippo pathway activation promotes green-sensitive PR fate at the expense of blue-sensitive PRs. Here, using a sensitized triple heterozygote-based genetic screening approach, we report the identification of the single Drosophila zonula occludens-1 (ZO-1) protein Polychaetoid (Pyd) as a new regulator of the Hippo pathway during the blue- and green-sensitive PR subtype binary fate choice. We demonstrate that Pyd acts upstream of the core components and the upstream regulator Pez in the Hippo pathway. Furthermore, We found that Pyd represses the activity of Su(dx), a E3 ligase that negatively regulates Pez and can physically interact with Pyd, during PR subtype fate specification. Together, our results identify a new mechanism underlying the Hippo signaling pathway in post-mitotic neuronal fate specification.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / metabolism*
  • Heterozygote
  • Hippo Kinases
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Protein Serine-Threonine Kinases / metabolism*
  • Signal Transduction
  • Tight Junction Proteins / genetics
  • Tight Junction Proteins / metabolism*
  • Zonula Occludens-1 Protein / genetics
  • Zonula Occludens-1 Protein / metabolism*

Substances

  • Drosophila Proteins
  • Intracellular Signaling Peptides and Proteins
  • Protein Serine-Threonine Kinases
  • Tight Junction Proteins
  • Zonula Occludens-1 Protein
  • pyd protein, Drosophila
  • hpo protein, Drosophila
  • Hippo Kinases