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Heterophilic and homophilic cadherin interactions in intestinal intermicrovillar links are species dependent

Enterocytes are specialized epithelial cells lining the luminal surface of the small intestine that build densely packed arrays of microvilli known as brush borders. These microvilli drive nutrient absorption and are arranged in a hexagonal pattern maintained by intermicrovillar links formed by 2 no...

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Autores principales: Gray, Michelle E., Johnson, Zachary R., Modak, Debadrita, Tamilselvan, Elakkiya, Tyska, Matthew J., Sotomayor, Marcos
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8691648/
https://www.ncbi.nlm.nih.gov/pubmed/34871294
http://dx.doi.org/10.1371/journal.pbio.3001463
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author Gray, Michelle E.
Johnson, Zachary R.
Modak, Debadrita
Tamilselvan, Elakkiya
Tyska, Matthew J.
Sotomayor, Marcos
author_facet Gray, Michelle E.
Johnson, Zachary R.
Modak, Debadrita
Tamilselvan, Elakkiya
Tyska, Matthew J.
Sotomayor, Marcos
author_sort Gray, Michelle E.
collection PubMed
description Enterocytes are specialized epithelial cells lining the luminal surface of the small intestine that build densely packed arrays of microvilli known as brush borders. These microvilli drive nutrient absorption and are arranged in a hexagonal pattern maintained by intermicrovillar links formed by 2 nonclassical members of the cadherin superfamily of calcium-dependent cell adhesion proteins: protocadherin-24 (PCDH24, also known as CDHR2) and the mucin-like protocadherin (CDHR5). The extracellular domains of these proteins are involved in heterophilic and homophilic interactions important for intermicrovillar function, yet the structural determinants of these interactions remain unresolved. Here, we present X-ray crystal structures of the PCDH24 and CDHR5 extracellular tips and analyze their species-specific features relevant for adhesive interactions. In parallel, we use binding assays to identify the PCDH24 and CDHR5 domains involved in both heterophilic and homophilic adhesion for human and mouse proteins. Our results suggest that homophilic and heterophilic interactions involving PCDH24 and CDHR5 are species dependent with unique and distinct minimal adhesive units.
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spelling pubmed-86916482021-12-22 Heterophilic and homophilic cadherin interactions in intestinal intermicrovillar links are species dependent Gray, Michelle E. Johnson, Zachary R. Modak, Debadrita Tamilselvan, Elakkiya Tyska, Matthew J. Sotomayor, Marcos PLoS Biol Research Article Enterocytes are specialized epithelial cells lining the luminal surface of the small intestine that build densely packed arrays of microvilli known as brush borders. These microvilli drive nutrient absorption and are arranged in a hexagonal pattern maintained by intermicrovillar links formed by 2 nonclassical members of the cadherin superfamily of calcium-dependent cell adhesion proteins: protocadherin-24 (PCDH24, also known as CDHR2) and the mucin-like protocadherin (CDHR5). The extracellular domains of these proteins are involved in heterophilic and homophilic interactions important for intermicrovillar function, yet the structural determinants of these interactions remain unresolved. Here, we present X-ray crystal structures of the PCDH24 and CDHR5 extracellular tips and analyze their species-specific features relevant for adhesive interactions. In parallel, we use binding assays to identify the PCDH24 and CDHR5 domains involved in both heterophilic and homophilic adhesion for human and mouse proteins. Our results suggest that homophilic and heterophilic interactions involving PCDH24 and CDHR5 are species dependent with unique and distinct minimal adhesive units. Public Library of Science 2021-12-06 /pmc/articles/PMC8691648/ /pubmed/34871294 http://dx.doi.org/10.1371/journal.pbio.3001463 Text en © 2021 Gray et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Gray, Michelle E.
Johnson, Zachary R.
Modak, Debadrita
Tamilselvan, Elakkiya
Tyska, Matthew J.
Sotomayor, Marcos
Heterophilic and homophilic cadherin interactions in intestinal intermicrovillar links are species dependent
title Heterophilic and homophilic cadherin interactions in intestinal intermicrovillar links are species dependent
title_full Heterophilic and homophilic cadherin interactions in intestinal intermicrovillar links are species dependent
title_fullStr Heterophilic and homophilic cadherin interactions in intestinal intermicrovillar links are species dependent
title_full_unstemmed Heterophilic and homophilic cadherin interactions in intestinal intermicrovillar links are species dependent
title_short Heterophilic and homophilic cadherin interactions in intestinal intermicrovillar links are species dependent
title_sort heterophilic and homophilic cadherin interactions in intestinal intermicrovillar links are species dependent
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8691648/
https://www.ncbi.nlm.nih.gov/pubmed/34871294
http://dx.doi.org/10.1371/journal.pbio.3001463
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