Influence of aminoacyl-tRNA synthetase complex-interacting multifunctional protein 1 on epithelial differentiation and organization during lung development.

Szczegóły
Abstrakt

Tytuł:: Influence of aminoacyl-tRNA synthetase complex-interacting multifunctional protein 1 on epithelial differentiation and organization during lung development.
Autorzy:: Lee DD; Department of Anatomy, Cell Biology and Physiology, Indiana University School of Medicine, South Bend, Indiana.; Department of Pediatrics, Indiana University School of Medicine, South Bend, Indiana.
Hochstetler A; Department of Anatomy, Cell Biology and Physiology, Indiana University School of Medicine, South Bend, Indiana.; Department of Pediatrics, Indiana University School of Medicine, South Bend, Indiana.
Sah E; Department of Applied and Computational Mathematics and Statistics, University of Notre Dame, South Bend, Indiana.
Xu H; Department of Pediatrics, University of Texas-Southwestern, Dallas, Texas.
Lowe CW; Department of Anatomy, Cell Biology and Physiology, Indiana University School of Medicine, South Bend, Indiana.; Department of Pediatrics, Indiana University School of Medicine, South Bend, Indiana.
Santiaguel S; Department of Anatomy, Cell Biology and Physiology, Indiana University School of Medicine, South Bend, Indiana.; Department of Pediatrics, Indiana University School of Medicine, South Bend, Indiana.
Thornton JL; Department of Pediatrics, University of Texas-Southwestern, Dallas, Texas.
Pajakowski A; Department of Anatomy, Cell Biology and Physiology, Indiana University School of Medicine, South Bend, Indiana.; Department of Pediatrics, Indiana University School of Medicine, South Bend, Indiana.
Schwarz MA; Department of Anatomy, Cell Biology and Physiology, Indiana University School of Medicine, South Bend, Indiana.; Department of Pediatrics, Indiana University School of Medicine, South Bend, Indiana.; Department of Biological Sciences, University of Notre Dame, South Bend, Indiana.; Department of Pediatrics, University of Texas-Southwestern, Dallas, Texas.
Źródło:: American journal of physiology. Lung cellular and molecular physiology [Am J Physiol Lung Cell Mol Physiol] 2020 Aug 01; Vol. 319 (2), pp. L369-L379. Date of Electronic Publication: 2020 Jun 24.
Typ publikacji:: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
Język:: English
Imprint Name(s):: Original Publication: Bethesda, MD : American Physiological Society, c1989-
MeSH Terms:: Amino Acyl-tRNA Synthetases/*metabolism
Cell Differentiation/*physiology
Cytokines/*metabolism
Epithelial Cells/*metabolism
Epithelial Cells/*physiology
Lung/*metabolism
Lung/*physiology
Actins/metabolism ; Animals ; Cell Membrane/metabolism ; Cell Membrane/physiology ; Female ; Intercellular Junctions/metabolism ; Intercellular Junctions/physiology ; Male ; Mice ; Mice, Inbred C57BL
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Grant Information:: UL1TR001108 International HHS | NIH | National Center for Advancing Translational Sciences (NCATS); T32 HL091816 United States HL NHLBI NIH HHS; UL1 TR001108 United States TR NCATS NIH HHS; R21 HD090227 United States HD NICHD NIH HHS; R01 HL114977 United States HL NHLBI NIH HHS
Contributed Indexing:: Keywords: AIMP1; F-actin; alveolar; lung development; phosphoinositide(s)
Substance Nomenclature:: 0 (Actins)
0 (Aimp1 protein, mouse)
0 (Cytokines)
EC 6.1.1.- (Amino Acyl-tRNA Synthetases)
Entry Date(s):: Date Created: 20200625 Date Completed: 20201120 Latest Revision: 20210802
Update Code:: 20240105
PubMed Central ID:: PMC7473932
DOI:: 10.1152/ajplung.00518.2019
PMID:: 32579851
: Czasopismo naukowe

Proper development of the respiratory bronchiole and alveolar epithelium proceeds through coordinated cross talk between the interface of epithelium and neighboring mesenchyme. Signals that facilitate and coordinate the cross talk as the bronchial forming canalicular stage transitions to construction of air-exchanging capillary-alveoli niche in the alveolar stage are poorly understood. Expressed within this decisive region, levels of aminoacyl-tRNA synthetase complex-interacting multifunctional protein 1 (AIMP1) inversely correlate with the maturation of the lung. The present study addresses the role of AIMP1 in lung development through the generation and characterization of Aimp1 -/- mutant mice. Mating of Aimp1 +/- produced offspring in expected Mendelian ratios throughout embryonic development. However, newborn Aimp1 -/- pups exhibited neonatal lethality with mild cyanosis. Imaging both structure and ultrastructure of Aimp1 -/- lungs showed disorganized bronchial epithelium, decreased type I but not type II cell differentiation, increased distal vessels, and disruption of E-cadherin deposition in cell-cell junctions. Supporting the in vivo findings of disrupted epithelial cell-cell junctions, in vitro biochemical experiments show that a portion of AIMP1 binds to phosphoinositides, the lipid anchor of proteins that have a fundamental role in both cellular membrane and actin cytoskeleton organization; a dramatic disruption in F-actin cytoskeleton was observed in Aimp1 -/- mouse embryonic fibroblasts. Such observed structural defects may lead to disrupted cell-cell boundaries. Together, these results suggest a requirement of AIMP1 in epithelial cell differentiation in proper lung development.

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