title: Yes-associated protein impacts adherens junction assembly through regulating actin cytoskeleton organization.
abstract: The Hippo pathway effector Yes-associated protein (YAP) regulates liver size by promoting cell proliferation and inhibiting apoptosis. However, recent in vivo studies suggest that YAP has important cellular functions other than controlling proliferation and apoptosis. Transgenic YAP expression in mouse hepatocytes results in severe jaundice. A possible explanation for the jaundice could be defects in adherens junctions that prevent bile from leaking into the blood stream. Indeed, immunostaining of E-cadherin and electron microscopic examination of bile canaliculi of Yap transgenic livers revealed abnormal adherens junction structures. Using primary hepatocytes from Yap transgenic livers and Yap knockout livers, we found that YAP antagonizes E-cadherin-mediated cell-cell junction assembly by regulating the cellular actin architecture, including its mechanical properties (elasticity and cortical tension). Mechanistically, we found that YAP promoted contractile actin structure formation by upregulating nonmuscle myosin light chain expression and cellular ATP generation. Thus, by modulating actomyosin organization, YAP may influence many actomyosin-dependent cellular characteristics, including adhesion, membrane protrusion, spreading, morphology, and cortical tension and elasticity, which in turn determine cell differentiation and tissue morphogenesis.
authors.affiliation: Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland;
authors.forename: Haibo
authors.initials: H
authors.lastname: Bai
authors.affiliation: Institute of Biomedical Sciences (IBS), Fudan University, Shanghai, People's Republic of China; and Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland;
authors.forename: Qingfeng
authors.initials: Q
authors.lastname: Zhu
authors.affiliation: Department of Cell Biology, Johns Hopkins School of Medicine, Baltimore, Maryland;
authors.forename: Alexandra
authors.initials: A
authors.lastname: Surcel
authors.affiliation: Department of Cell Biology, Johns Hopkins School of Medicine, Baltimore, Maryland;
authors.forename: Tianzhi
authors.initials: T
authors.lastname: Luo
authors.affiliation: Department of Cell Biology, Johns Hopkins School of Medicine, Baltimore, Maryland;
authors.forename: Yixin
authors.initials: Y
authors.lastname: Ren
authors.affiliation: Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland;
authors.forename: Bin
authors.initials: B
authors.lastname: Guan
authors.affiliation: Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland;
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Research, Central Texas Veterans Health Care System, Temple, Texas; Department of Medicine, Division of Gastroenterology, Texas A&M Health Science Center College of Medicine, Temple, Texas; and Baylor Scott & White Health Digestive Disease Research Center, Temple, Texas.
authors.forename: Nan
authors.initials: N
authors.lastname: Wu
authors.affiliation: Department of Pathology, University of Chicago, Chicago, Illinois; and.
authors.forename: Nora Eve
authors.initials: NE
authors.lastname: Joseph
authors.affiliation: Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland;
authors.forename: Tian-Li
authors.initials: TL
authors.lastname: Wang
authors.affiliation: Department of Molecular Biology and Genetics, Howard Hughes Medical Institute, Johns Hopkins School of Medicine, Baltimore, Maryland;
authors.forename: Nailing
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Department of Molecular Biology and Genetics, Howard Hughes Medical Institute, Johns Hopkins School of Medicine, Baltimore, Maryland;
authors.forename: Duojia
authors.initials: D
authors.lastname: Pan
authors.affiliation: Research, Central Texas Veterans Health Care System, Temple, Texas; Department of Medicine, Division of Gastroenterology, Texas A&M Health Science Center College of Medicine, Temple, Texas; and Baylor Scott & White Health Digestive Disease Research Center, Temple, Texas.
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Alpini
authors.affiliation: Department of Cell Biology, Johns Hopkins School of Medicine, Baltimore, Maryland;
authors.forename: Douglas N
authors.initials: DN
authors.lastname: Robinson
authors.affiliation: Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland; rander54@jhmi.edu.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Anders
mesh_terms: D008841:Actin Cytoskeleton / Q000502:physiology*; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D022005:Adherens Junctions / Q000502:physiology*; D000818:Animals; D015820:Cadherins; D018797:Cell Cycle Proteins; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D022781:Hepatocytes / Q000502:physiology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D000091262:TEA Domain Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D000091102:YAP-Signaling Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015820:Cadherins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D010750:Phosphoproteins; D000091262:TEA Domain Transcription Factors; C486310:Tead2 protein, mouse; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins; C486223:Yap1 protein, mouse
keywords: YAP; actin cytoskeleton; adherens junctions