@article{6563bb51aef4479b936c2a266836ee10,
title = "Ptp61F integrates Hippo, TOR, and actomyosin pathways to control three-dimensional organ size",
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.",
keywords = "CP: Developmental biology, Drosophila, Expanded, Hippo, TOR, endocytosis, ptp61F, tension",
author = "Peng Liu and Yifan Guo and Wenyan Xu and Sha Song and Xiaoqin Li and Xing Wang and Jinyu Lu and Xiaowei Guo and Richardson, {Helena E.} and Xianjue Ma",
note = "Funding Information: We are grateful to Shian Wu, Duojia Pan, Georg Halder, Jessica E. Treisman, Jin Jiang, Richard Fehon, Tzu-Ching Meng, Peter Bryant, Seth S. Blair, Tian Xu, Bruce Hay, Aurelio A. Teleman, Jack E. Dixon, Jongkyeong Chung, Marcos Gonz{\'a}lez-Gait{\'a}n, Jos{\'e} C. Pastor-Pareja, Hansong Deng, and Elisabeth Knust for generously sharing fly stocks and reagents. We thank the BDSC, VDRC, NIG-FLY, and DSHB for stocks and antibodies. We thank Li He, Xiaolong Yang, Hai Song, and Shian Wu for helpful discussions. X.M. is funded by Westlake University and the National Natural Science Foundation of China (32170824), Westlake Laboratory of Life Sciences and Biomedicine (10128A092001), and “Team for Growth Control and Size Innovative Research” (201804016). X.M. conceived, designed, and supervised the study; P.L. Y.G. W.X. S.S. J.L. X.L. and X.W. performed the experiments; X.M. P.L. Y.G. X.G. and H.E.R. analyzed the data. X.M. wrote the manuscript with input from P.L. and H.E.R. The authors declare no competing interests. Funding Information: We are grateful to Shian Wu, Duojia Pan, Georg Halder, Jessica E. Treisman, Jin Jiang, Richard Fehon, Tzu-Ching Meng, Peter Bryant, Seth S. Blair, Tian Xu, Bruce Hay, Aurelio A. Teleman, Jack E. Dixon, Jongkyeong Chung, Marcos Gonz{\'a}lez-Gait{\'a}n, Jos{\'e} C. Pastor-Pareja, Hansong Deng, and Elisabeth Knust for generously sharing fly stocks and reagents. We thank the BDSC, VDRC, NIG-FLY, and DSHB for stocks and antibodies. We thank Li He, Xiaolong Yang, Hai Song, and Shian Wu for helpful discussions. X.M. is funded by Westlake University and the National Natural Science Foundation of China ( 32170824 ), Westlake Laboratory of Life Sciences and Biomedicine ( 10128A092001 ), and “ Team for Growth Control and Size Innovative Research ” ( 201804016 ). Publisher Copyright: {\textcopyright} 2022 The Author(s)",
year = "2022",
month = nov,
day = "15",
doi = "10.1016/j.celrep.2022.111640",
language = "English (US)",
volume = "41",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "7",
}