Ptp61F integrates Hippo, TOR, and actomyosin pathways to control three-dimensional organ size

Peng Liu, Yifan Guo, Wenyan Xu, Sha Song, Xiaoqin Li, Xing Wang, Jinyu Lu, Xiaowei Guo, Helena E. Richardson, Xianjue Ma

Research output: Contribution to journalArticlepeer-review

Abstract

Precise organ size control is fundamental for all metazoans, but how organ size is controlled in a three-dimensional (3D) way remains largely unexplored at the molecular level. Here, we screen and identify Drosophila Ptp61F as a pivotal regulator of organ size that integrates the Hippo pathway, TOR pathway, and actomyosin machinery. Pathologically, Ptp61F loss synergizes with RasV12 to induce tumorigenesis. Physiologically, Ptp61F depletion increases body size and drives neoplastic intestinal tumor formation and stem cell proliferation. Ptp61F also regulates cell contractility and myosin activation and controls 3D cell shape by reducing cell height and horizontal cell size. Mechanistically, Ptp61F forms a complex with Expanded (Ex) and increases endosomal localization of Ex and Yki. Furthermore, we demonstrate that PTPN2, the conserved human ortholog of Ptp61F, can functionally substitute for Ptp61F in Drosophila. Our work defines Ptp61F as an essential determinant that controls 3D organ size under both physiological and pathological conditions.

Original languageEnglish (US)
Article number111640
JournalCell Reports
Volume41
Issue number7
DOIs
StatePublished - Nov 15 2022

Keywords

  • CP: Developmental biology
  • Drosophila
  • Expanded
  • Hippo
  • TOR
  • endocytosis
  • ptp61F
  • tension

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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