Defining functional interactions during biogenesis of epithelial junctions
In spite of extensive recent progress, a comprehensive understanding of how actin cytoskeleton remodelling supports stable junctions remains to be established. Here we design a platform that integrates actin functions with optimized phenotypic clustering and identify new cytoskeletal proteins, their...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Journal article |
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Nature Publishing Group
2016
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| _version_ | 1797082243764584448 |
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| author | Erasmus, J Bruche, S Pizarro, L Maimari, N Pogglioli, T Tomlinson, C Lees, J Zavilina, I Wheeler, A Alberts, A Russo, A Braga, V |
| author_facet | Erasmus, J Bruche, S Pizarro, L Maimari, N Pogglioli, T Tomlinson, C Lees, J Zavilina, I Wheeler, A Alberts, A Russo, A Braga, V |
| author_sort | Erasmus, J |
| collection | OXFORD |
| description | In spite of extensive recent progress, a comprehensive understanding of how actin cytoskeleton remodelling supports stable junctions remains to be established. Here we design a platform that integrates actin functions with optimized phenotypic clustering and identify new cytoskeletal proteins, their functional hierarchy and pathways that modulate E-cadherin adhesion. Depletion of EEF1A, an actin bundling protein, increases E-cadherin levels at junctions without a corresponding reinforcement of cell–cell contacts. This unexpected result reflects a more dynamic and mobile junctional actin in EEF1A-depleted cells. A partner for EEF1A in cadherin contact maintenance is the formin DIAPH2, which interacts with EEF1A. In contrast, depletion of either the endocytic regulator TRIP10 or the Rho GTPase activator VAV2 reduces E-cadherin levels at junctions. TRIP10 binds to and requires VAV2 function for its junctional localization. Overall, we present new conceptual insights on junction stabilization, which integrate known and novel pathways with impact for epithelial morphogenesis, homeostasis and diseases. |
| first_indexed | 2024-03-07T01:25:21Z |
| format | Journal article |
| id | oxford-uuid:91c8917b-2502-4d1b-aa75-79f46f6575ba |
| institution | University of Oxford |
| last_indexed | 2024-03-07T01:25:21Z |
| publishDate | 2016 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | oxford-uuid:91c8917b-2502-4d1b-aa75-79f46f6575ba2022-03-26T23:20:59ZDefining functional interactions during biogenesis of epithelial junctionsJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:91c8917b-2502-4d1b-aa75-79f46f6575baSymplectic Elements at OxfordNature Publishing Group2016Erasmus, JBruche, SPizarro, LMaimari, NPogglioli, TTomlinson, CLees, JZavilina, IWheeler, AAlberts, ARusso, ABraga, VIn spite of extensive recent progress, a comprehensive understanding of how actin cytoskeleton remodelling supports stable junctions remains to be established. Here we design a platform that integrates actin functions with optimized phenotypic clustering and identify new cytoskeletal proteins, their functional hierarchy and pathways that modulate E-cadherin adhesion. Depletion of EEF1A, an actin bundling protein, increases E-cadherin levels at junctions without a corresponding reinforcement of cell–cell contacts. This unexpected result reflects a more dynamic and mobile junctional actin in EEF1A-depleted cells. A partner for EEF1A in cadherin contact maintenance is the formin DIAPH2, which interacts with EEF1A. In contrast, depletion of either the endocytic regulator TRIP10 or the Rho GTPase activator VAV2 reduces E-cadherin levels at junctions. TRIP10 binds to and requires VAV2 function for its junctional localization. Overall, we present new conceptual insights on junction stabilization, which integrate known and novel pathways with impact for epithelial morphogenesis, homeostasis and diseases. |
| spellingShingle | Erasmus, J Bruche, S Pizarro, L Maimari, N Pogglioli, T Tomlinson, C Lees, J Zavilina, I Wheeler, A Alberts, A Russo, A Braga, V Defining functional interactions during biogenesis of epithelial junctions |
| title | Defining functional interactions during biogenesis of epithelial junctions |
| title_full | Defining functional interactions during biogenesis of epithelial junctions |
| title_fullStr | Defining functional interactions during biogenesis of epithelial junctions |
| title_full_unstemmed | Defining functional interactions during biogenesis of epithelial junctions |
| title_short | Defining functional interactions during biogenesis of epithelial junctions |
| title_sort | defining functional interactions during biogenesis of epithelial junctions |
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