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N-glycosylation controls the function of junctional adhesion molecule-A
Junctional adhesion molecule-A (JAM-A) is an adherens and tight junction protein expressed by endothelial and epithelial cells. JAM-A serves many roles and contributes to barrier function and cell migration and motility, and it also acts as a ligand for the leukocyte receptor LFA-1. JAM-A is reporte...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4569312/ https://www.ncbi.nlm.nih.gov/pubmed/26224316 http://dx.doi.org/10.1091/mbc.E14-12-1604 |
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author | Scott, David W. Tolbert, Caitlin E. Graham, David M. Wittchen, Erika Bear, James E. Burridge, Keith |
author_facet | Scott, David W. Tolbert, Caitlin E. Graham, David M. Wittchen, Erika Bear, James E. Burridge, Keith |
author_sort | Scott, David W. |
collection | PubMed |
description | Junctional adhesion molecule-A (JAM-A) is an adherens and tight junction protein expressed by endothelial and epithelial cells. JAM-A serves many roles and contributes to barrier function and cell migration and motility, and it also acts as a ligand for the leukocyte receptor LFA-1. JAM-A is reported to contain N-glycans, but the extent of this modification and its contribution to the protein’s functions are unknown. We show that human JAM-A contains a single N-glycan at N185 and that this residue is conserved across multiple mammalian species. A glycomutant lacking all N-glycans, N185Q, is able to reach the cell surface but exhibits decreased protein half-life compared with the wild- type protein. N-glycosylation of JAM-A is required for the protein’s ability to reinforce barrier function and contributes to Rap1 activity. We further show that glycosylation of N185 is required for JAM-A–mediated reduction of cell migration. Finally, we show that N-glycosylation of JAM-A regulates leukocyte adhesion and LFA-1 binding. These findings identify N-glycosylation as critical for JAM-A’s many functions. |
format | Online Article Text |
id | pubmed-4569312 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-45693122015-11-30 N-glycosylation controls the function of junctional adhesion molecule-A Scott, David W. Tolbert, Caitlin E. Graham, David M. Wittchen, Erika Bear, James E. Burridge, Keith Mol Biol Cell Articles Junctional adhesion molecule-A (JAM-A) is an adherens and tight junction protein expressed by endothelial and epithelial cells. JAM-A serves many roles and contributes to barrier function and cell migration and motility, and it also acts as a ligand for the leukocyte receptor LFA-1. JAM-A is reported to contain N-glycans, but the extent of this modification and its contribution to the protein’s functions are unknown. We show that human JAM-A contains a single N-glycan at N185 and that this residue is conserved across multiple mammalian species. A glycomutant lacking all N-glycans, N185Q, is able to reach the cell surface but exhibits decreased protein half-life compared with the wild- type protein. N-glycosylation of JAM-A is required for the protein’s ability to reinforce barrier function and contributes to Rap1 activity. We further show that glycosylation of N185 is required for JAM-A–mediated reduction of cell migration. Finally, we show that N-glycosylation of JAM-A regulates leukocyte adhesion and LFA-1 binding. These findings identify N-glycosylation as critical for JAM-A’s many functions. The American Society for Cell Biology 2015-09-15 /pmc/articles/PMC4569312/ /pubmed/26224316 http://dx.doi.org/10.1091/mbc.E14-12-1604 Text en © 2015 Scott 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 for Cell Biology. |
spellingShingle | Articles Scott, David W. Tolbert, Caitlin E. Graham, David M. Wittchen, Erika Bear, James E. Burridge, Keith N-glycosylation controls the function of junctional adhesion molecule-A |
title | N-glycosylation controls the function of junctional adhesion molecule-A |
title_full | N-glycosylation controls the function of junctional adhesion molecule-A |
title_fullStr | N-glycosylation controls the function of junctional adhesion molecule-A |
title_full_unstemmed | N-glycosylation controls the function of junctional adhesion molecule-A |
title_short | N-glycosylation controls the function of junctional adhesion molecule-A |
title_sort | n-glycosylation controls the function of junctional adhesion molecule-a |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4569312/ https://www.ncbi.nlm.nih.gov/pubmed/26224316 http://dx.doi.org/10.1091/mbc.E14-12-1604 |
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