title: Distinct polarity cues direct Taz/Yap and TGFβ receptor localization to differentially control TGFβ-induced Smad signaling.
abstract: We and others have shown that the Hippo pathway effectors TAZ and YAP direct Smad activity to regulate TGFβ family-induced cellular responses in stem cell and cancer biology. In polarized epithelial cells we showed that the Crumbs complex promotes Hippo-dependent cytoplasmic TAZ/YAP localization that restricts TGFβ-induced Smad nuclear accumulation and activity. In this Developmental Cell issue, basal-lateral restriction of TGFβ receptors is proposed as the sole mechanism suppressing Smad signaling in epithelial cells. Here we show that basal recruitment of TGFβ receptors occurs subsequent to Hippo-dependent suppression of Smad activity by cytoplasmic TAZ/YAP. Our results demonstrate that receptor sequestration and Hippo control of activated Smads are distinct events regulating TGFβ signaling in polarized epithelia and raise interesting questions about the function of these pathways in controlling Smad signaling in development, homeostasis, and disease. This Matters Arising Response addresses the Nallet-Staub et al. (2015) Matters Arising, published concurrently in Developmental Cell.
authors.affiliation: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, M5G 1X5 ON, Canada.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Narimatsu
authors.affiliation: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, M5G 1X5 ON, Canada.
authors.forename: Payman
authors.initials: P
authors.lastname: Samavarchi-Tehrani
authors.affiliation: Department of Biochemistry, Boston University School of Medicine, Boston, MA 02118, USA. Electronic address: xvarelas@bu.edu.
authors.forename: Xaralabos
authors.initials: X
authors.lastname: Varelas
authors.affiliation: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, M5G 1X5 ON, Canada; Department of Molecular Genetics, University of Toronto, Toronto, M5S 1A8 ON, Canada. Electronic address: wrana@lunenfeld.ca.
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Wrana
mesh_terms: D000217:Acyltransferases; D015153:Blotting, Western; D018797:Cell Cycle Proteins; D016764:Cell Polarity; D049109:Cell Proliferation; D002478:Cells, Cultured; D005455:Fluorescent Antibody Technique; D006801:Humans; D018613:Microscopy, Confocal; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D036122:Receptor, EphA4 / Q000378:metabolism*; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism*; D015398:Signal Transduction; D051785:Smad Proteins / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; D018125:Receptors, Transforming Growth Factor beta; D051785:Smad Proteins; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; C456659:YY1AP1 protein, human; D000217:Acyltransferases; C108675:TAFAZZIN protein, human; D036122:Receptor, EphA4