title: Talin1 is required for cardiac Z-disk stabilization and endothelial integrity in zebrafish.
abstract: Talin (tln) binds and activates integrins to couple extracellular matrix-bound integrins to the cytoskeleton; however, its role in heart development is not well characterized. We identified the defective gene and the resulting cardiovascular phenotypes in zebrafish tln1(fl02k) mutants. The ethylnitrosourea-induced fl02k mutant showed heart failure, brain hemorrhage, and diminished cardiac and vessel lumens at 52 h post fertilization. Positional cloning revealed a nonsense mutation of tln1 in this mutant. tln1, but neither tln2 nor -2a, was dominantly expressed in the heart and vessels. Unlike tln1 and -2 in the mouse heart, the unique tln1 expression in the heart enabled us, for the first time, to determine the critical roles of Tln1 in the maintenance of cardiac sarcomeric Z-disks and endothelial/endocardial cell integrity, partly through regulating F-actin networks in zebrafish. The similar expression profiles of tln1 and integrin β1b (itgb1b) and synergistic function of the 2 genes revealed that itgb1b is a potential partner for tln1 in the stabilization of cardiac Z-disks and vessel lumens. Taken together, the results of this work suggest that Tln1-mediated Itgβ1b plays a crucial role in maintaining cardiac sarcomeric Z-disks and endothelial/endocardial cell integrity in zebrafish and may also help to gain molecular insights into congenital heart diseases.
authors: *Beijing Key Laboratory of Cardiometabolic Molecular Medicine and State Key Laboratory of Natural and Biomimetic Drugs, Institute of Molecular Medicine, Peking University, Beijing, China; Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA; Department of Medical Pharmacology and Department of Physiology, School of Medicine, University of Missouri, Columbia, Missouri, USA; and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors: Qing
authors: Q
authors: Wu
authors: *Beijing Key Laboratory of Cardiometabolic Molecular Medicine and State Key Laboratory of Natural and Biomimetic Drugs, Institute of Molecular Medicine, Peking University, Beijing, China; Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA; Department of Medical Pharmacology and Department of Physiology, School of Medicine, University of Missouri, Columbia, Missouri, USA; and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors: Jiaojiao
authors: J
authors: Zhang
authors: *Beijing Key Laboratory of Cardiometabolic Molecular Medicine and State Key Laboratory of Natural and Biomimetic Drugs, Institute of Molecular Medicine, Peking University, Beijing, China; Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA; Department of Medical Pharmacology and Department of Physiology, School of Medicine, University of Missouri, Columbia, Missouri, USA; and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors: Wonshill
authors: W
authors: Koh
authors: *Beijing Key Laboratory of Cardiometabolic Molecular Medicine and State Key Laboratory of Natural and Biomimetic Drugs, Institute of Molecular Medicine, Peking University, Beijing, China; Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA; Department of Medical Pharmacology and Department of Physiology, School of Medicine, University of Missouri, Columbia, Missouri, USA; and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors: Qingming
authors: Q
authors: Yu
authors: *Beijing Key Laboratory of Cardiometabolic Molecular Medicine and State Key Laboratory of Natural and Biomimetic Drugs, Institute of Molecular Medicine, Peking University, Beijing, China; Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA; Department of Medical Pharmacology and Department of Physiology, School of Medicine, University of Missouri, Columbia, Missouri, USA; and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors: Xiaojun
authors: X
authors: Zhu
authors: *Beijing Key Laboratory of Cardiometabolic Molecular Medicine and State Key Laboratory of Natural and Biomimetic Drugs, Institute of Molecular Medicine, Peking University, Beijing, China; Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA; Department of Medical Pharmacology and Department of Physiology, School of Medicine, University of Missouri, Columbia, Missouri, USA; and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors: Adam
authors: A
authors: Amsterdam
authors: *Beijing Key Laboratory of Cardiometabolic Molecular Medicine and State Key Laboratory of Natural and Biomimetic Drugs, Institute of Molecular Medicine, Peking University, Beijing, China; Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA; Department of Medical Pharmacology and Department of Physiology, School of Medicine, University of Missouri, Columbia, Missouri, USA; and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors: George E
authors: GE
authors: Davis
authors: *Beijing Key Laboratory of Cardiometabolic Molecular Medicine and State Key Laboratory of Natural and Biomimetic Drugs, Institute of Molecular Medicine, Peking University, Beijing, China; Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA; Department of Medical Pharmacology and Department of Physiology, School of Medicine, University of Missouri, Columbia, Missouri, USA; and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors: M Amin
authors: MA
authors: Arnaout
authors: *Beijing Key Laboratory of Cardiometabolic Molecular Medicine and State Key Laboratory of Natural and Biomimetic Drugs, Institute of Molecular Medicine, Peking University, Beijing, China; Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA; Department of Medical Pharmacology and Department of Physiology, School of Medicine, University of Missouri, Columbia, Missouri, USA; and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA jingwei_xiong@pku.edu.cn.
authors: Jing-Wei
authors: JW
authors: Xiong
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D004730:Endothelium, Vascular / Q000166:cytology*; D006321:Heart / Q000196:embryology*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D019012:Integrin beta1 / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D017386:Sequence Homology, Amino Acid; D016608:Talin / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D015027:Zebrafish / Q000196:embryology
chemical_list: D019012:Integrin beta1; D016608:Talin
keywords: cardiac sarcomere; cardiovascular development; itgb1b; tln1