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Bves and NDRG4 regulate directional epicardial cell migration through autocrine extracellular matrix deposition
Directional cell movement is universally required for tissue morphogenesis. Although it is known that cell/matrix interactions are essential for directional movement in heart development, the mechanisms governing these interactions require elucidation. Here we demonstrate that a novel protein/protei...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3826988/ https://www.ncbi.nlm.nih.gov/pubmed/24048452 http://dx.doi.org/10.1091/mbc.E12-07-0539 |
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author | Benesh, Emily C. Miller, Paul M. Pfaltzgraff, Elise R. Grega-Larson, Nathan E. Hager, Hillary A. Sung, Bong Hwan Qu, Xianghu Baldwin, H. Scott Weaver, Alissa M. Bader, David M. |
author_facet | Benesh, Emily C. Miller, Paul M. Pfaltzgraff, Elise R. Grega-Larson, Nathan E. Hager, Hillary A. Sung, Bong Hwan Qu, Xianghu Baldwin, H. Scott Weaver, Alissa M. Bader, David M. |
author_sort | Benesh, Emily C. |
collection | PubMed |
description | Directional cell movement is universally required for tissue morphogenesis. Although it is known that cell/matrix interactions are essential for directional movement in heart development, the mechanisms governing these interactions require elucidation. Here we demonstrate that a novel protein/protein interaction between blood vessel epicardial substance (Bves) and N-myc downstream regulated gene 4 (NDRG4) is critical for regulation of epicardial cell directional movement, as disruption of this interaction randomizes migratory patterns. Our studies show that Bves/NDRG4 interaction is required for trafficking of internalized fibronectin through the “autocrine extracellular matrix (ECM) deposition” fibronectin recycling pathway. Of importance, we demonstrate that Bves/NDRG4-mediated fibronectin recycling is indeed essential for epicardial cell directional movement, thus linking these two cell processes. Finally, total internal reflectance fluorescence microscopy shows that Bves/NDRG4 interaction is required for fusion of recycling endosomes with the basal cell surface, providing a molecular mechanism of motility substrate delivery that regulates cell directional movement. This is the first evidence of a molecular function for Bves and NDRG4 proteins within broader subcellular trafficking paradigms. These data identify novel regulators of a critical vesicle-docking step required for autocrine ECM deposition and explain how Bves facilitates cell-microenvironment interactions in the regulation of epicardial cell–directed movement. |
format | Online Article Text |
id | pubmed-3826988 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-38269882014-01-30 Bves and NDRG4 regulate directional epicardial cell migration through autocrine extracellular matrix deposition Benesh, Emily C. Miller, Paul M. Pfaltzgraff, Elise R. Grega-Larson, Nathan E. Hager, Hillary A. Sung, Bong Hwan Qu, Xianghu Baldwin, H. Scott Weaver, Alissa M. Bader, David M. Mol Biol Cell Articles Directional cell movement is universally required for tissue morphogenesis. Although it is known that cell/matrix interactions are essential for directional movement in heart development, the mechanisms governing these interactions require elucidation. Here we demonstrate that a novel protein/protein interaction between blood vessel epicardial substance (Bves) and N-myc downstream regulated gene 4 (NDRG4) is critical for regulation of epicardial cell directional movement, as disruption of this interaction randomizes migratory patterns. Our studies show that Bves/NDRG4 interaction is required for trafficking of internalized fibronectin through the “autocrine extracellular matrix (ECM) deposition” fibronectin recycling pathway. Of importance, we demonstrate that Bves/NDRG4-mediated fibronectin recycling is indeed essential for epicardial cell directional movement, thus linking these two cell processes. Finally, total internal reflectance fluorescence microscopy shows that Bves/NDRG4 interaction is required for fusion of recycling endosomes with the basal cell surface, providing a molecular mechanism of motility substrate delivery that regulates cell directional movement. This is the first evidence of a molecular function for Bves and NDRG4 proteins within broader subcellular trafficking paradigms. These data identify novel regulators of a critical vesicle-docking step required for autocrine ECM deposition and explain how Bves facilitates cell-microenvironment interactions in the regulation of epicardial cell–directed movement. The American Society for Cell Biology 2013-11-15 /pmc/articles/PMC3826988/ /pubmed/24048452 http://dx.doi.org/10.1091/mbc.E12-07-0539 Text en © 2013 Benesh et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell Biology. |
spellingShingle | Articles Benesh, Emily C. Miller, Paul M. Pfaltzgraff, Elise R. Grega-Larson, Nathan E. Hager, Hillary A. Sung, Bong Hwan Qu, Xianghu Baldwin, H. Scott Weaver, Alissa M. Bader, David M. Bves and NDRG4 regulate directional epicardial cell migration through autocrine extracellular matrix deposition |
title | Bves and NDRG4 regulate directional epicardial cell migration through autocrine extracellular matrix deposition |
title_full | Bves and NDRG4 regulate directional epicardial cell migration through autocrine extracellular matrix deposition |
title_fullStr | Bves and NDRG4 regulate directional epicardial cell migration through autocrine extracellular matrix deposition |
title_full_unstemmed | Bves and NDRG4 regulate directional epicardial cell migration through autocrine extracellular matrix deposition |
title_short | Bves and NDRG4 regulate directional epicardial cell migration through autocrine extracellular matrix deposition |
title_sort | bves and ndrg4 regulate directional epicardial cell migration through autocrine extracellular matrix deposition |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3826988/ https://www.ncbi.nlm.nih.gov/pubmed/24048452 http://dx.doi.org/10.1091/mbc.E12-07-0539 |
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