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...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2021-12-01
|
| Series: | PLoS Biology |
| Online Access: | https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.3001463&type=printable |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850043067453669376 |
|---|---|
| author | Michelle E Gray Zachary R Johnson Debadrita Modak Elakkiya Tamilselvan Matthew J Tyska Marcos Sotomayor |
| author_facet | Michelle E Gray Zachary R Johnson Debadrita Modak Elakkiya Tamilselvan Matthew J Tyska Marcos Sotomayor |
| author_sort | Michelle E Gray |
| collection | DOAJ |
| 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 | Article |
| id | doaj-art-215bf8647f1b45f5ab50523fae5d7bc6 |
| institution | DOAJ |
| issn | 1544-9173 1545-7885 |
| language | English |
| publishDate | 2021-12-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Biology |
| spelling | doaj-art-215bf8647f1b45f5ab50523fae5d7bc62025-08-20T02:55:20ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852021-12-011912e300146310.1371/journal.pbio.3001463Heterophilic and homophilic cadherin interactions in intestinal intermicrovillar links are species dependent.Michelle E GrayZachary R JohnsonDebadrita ModakElakkiya TamilselvanMatthew J TyskaMarcos SotomayorEnterocytes 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.https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.3001463&type=printable |
| spellingShingle | Michelle E Gray Zachary R Johnson Debadrita Modak Elakkiya Tamilselvan Matthew J Tyska Marcos Sotomayor Heterophilic and homophilic cadherin interactions in intestinal intermicrovillar links are species dependent. PLoS Biology |
| 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 |
| url | https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.3001463&type=printable |
| work_keys_str_mv | AT michelleegray heterophilicandhomophiliccadherininteractionsinintestinalintermicrovillarlinksarespeciesdependent AT zacharyrjohnson heterophilicandhomophiliccadherininteractionsinintestinalintermicrovillarlinksarespeciesdependent AT debadritamodak heterophilicandhomophiliccadherininteractionsinintestinalintermicrovillarlinksarespeciesdependent AT elakkiyatamilselvan heterophilicandhomophiliccadherininteractionsinintestinalintermicrovillarlinksarespeciesdependent AT matthewjtyska heterophilicandhomophiliccadherininteractionsinintestinalintermicrovillarlinksarespeciesdependent AT marcossotomayor heterophilicandhomophiliccadherininteractionsinintestinalintermicrovillarlinksarespeciesdependent |