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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...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2021
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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. |
format | Online Article Text |
id | pubmed-8691648 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
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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