RRC ID 73095
Author Liu P, Guo Y, Xu W, Song S, Li X, Wang X, Lu J, Guo X, Richardson HE, Ma X.
Title Ptp61F integrates Hippo, TOR, and actomyosin pathways to control three-dimensional organ size.
Journal Cell Rep
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.
Volume 41(7)
Pages 111640
Published 2022-11-15
DOI 10.1016/j.celrep.2022.111640
PII S2211-1247(22)01511-X
PMID 36384105
MeSH Actomyosin* Animals Drosophila / metabolism Drosophila Proteins* / metabolism Humans Intracellular Signaling Peptides and Proteins / genetics Nuclear Proteins / metabolism Organ Size Protein Serine-Threonine Kinases / genetics Protein Tyrosine Phosphatases, Non-Receptor Trans-Activators / metabolism
IF 8.109