P62/SQSTM1 binds with claudin-2 to target for selective autophagy in stressed intestinal epithelium
Abstract Impaired autophagy promotes Inflammatory Bowel Disease (IBD). Claudin-2 is upregulated in IBD however its role in the pathobiology remains uncertain due to its complex regulation, including by autophagy. Irrespective, claudin-2 expression protects mice from DSS colitis. This study was under...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2023-07-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-023-05116-2 |
| _version_ | 1827894964657324032 |
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| author | Rizwan Ahmad Balawant Kumar Raju Lama Tamang Geoffrey A. Talmon Punita Dhawan Amar B. Singh |
| author_facet | Rizwan Ahmad Balawant Kumar Raju Lama Tamang Geoffrey A. Talmon Punita Dhawan Amar B. Singh |
| author_sort | Rizwan Ahmad |
| collection | DOAJ |
| description | Abstract Impaired autophagy promotes Inflammatory Bowel Disease (IBD). Claudin-2 is upregulated in IBD however its role in the pathobiology remains uncertain due to its complex regulation, including by autophagy. Irrespective, claudin-2 expression protects mice from DSS colitis. This study was undertaken to examine if an interplay between autophagy and claudin-2 protects from colitis and associated epithelial injury. Crypt culture and intestinal epithelial cells (IECs) are subjected to stress, including starvation or DSS, the chemical that induces colitis in-vivo. Autophagy flux, cell survival, co-immunoprecipitation, proximity ligation assay, and gene mutational studies are performed. These studies reveal that under colitis/stress conditions, claudin-2 undergoes polyubiquitination and P62/SQSTM1-assisted degradation through autophagy. Inhibiting autophagy-mediated claudin-2 degradation promotes cell death and thus suggest that claudin-2 degradation promotes autophagy flux to promote cell survival. Overall, these data inform for the previously undescribed role for claudin-2 in facilitating IECs survival under stress conditions, which can be harnessed for therapeutic advantages. |
| first_indexed | 2024-03-12T22:14:55Z |
| format | Article |
| id | doaj.art-6a56b71ff05b40b3a04d197b02b4e253 |
| institution | Directory Open Access Journal |
| issn | 2399-3642 |
| language | English |
| last_indexed | 2024-03-12T22:14:55Z |
| publishDate | 2023-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj.art-6a56b71ff05b40b3a04d197b02b4e2532023-07-23T11:22:49ZengNature PortfolioCommunications Biology2399-36422023-07-016111510.1038/s42003-023-05116-2P62/SQSTM1 binds with claudin-2 to target for selective autophagy in stressed intestinal epitheliumRizwan Ahmad0Balawant Kumar1Raju Lama Tamang2Geoffrey A. Talmon3Punita Dhawan4Amar B. Singh5Department of Biochemistry and Molecular Biology, University of Nebraska Medical CenterDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical CenterDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical CenterDepartment of Pathology and Microbiology, University of Nebraska Medical CenterDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical CenterDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical CenterAbstract Impaired autophagy promotes Inflammatory Bowel Disease (IBD). Claudin-2 is upregulated in IBD however its role in the pathobiology remains uncertain due to its complex regulation, including by autophagy. Irrespective, claudin-2 expression protects mice from DSS colitis. This study was undertaken to examine if an interplay between autophagy and claudin-2 protects from colitis and associated epithelial injury. Crypt culture and intestinal epithelial cells (IECs) are subjected to stress, including starvation or DSS, the chemical that induces colitis in-vivo. Autophagy flux, cell survival, co-immunoprecipitation, proximity ligation assay, and gene mutational studies are performed. These studies reveal that under colitis/stress conditions, claudin-2 undergoes polyubiquitination and P62/SQSTM1-assisted degradation through autophagy. Inhibiting autophagy-mediated claudin-2 degradation promotes cell death and thus suggest that claudin-2 degradation promotes autophagy flux to promote cell survival. Overall, these data inform for the previously undescribed role for claudin-2 in facilitating IECs survival under stress conditions, which can be harnessed for therapeutic advantages.https://doi.org/10.1038/s42003-023-05116-2 |
| spellingShingle | Rizwan Ahmad Balawant Kumar Raju Lama Tamang Geoffrey A. Talmon Punita Dhawan Amar B. Singh P62/SQSTM1 binds with claudin-2 to target for selective autophagy in stressed intestinal epithelium Communications Biology |
| title | P62/SQSTM1 binds with claudin-2 to target for selective autophagy in stressed intestinal epithelium |
| title_full | P62/SQSTM1 binds with claudin-2 to target for selective autophagy in stressed intestinal epithelium |
| title_fullStr | P62/SQSTM1 binds with claudin-2 to target for selective autophagy in stressed intestinal epithelium |
| title_full_unstemmed | P62/SQSTM1 binds with claudin-2 to target for selective autophagy in stressed intestinal epithelium |
| title_short | P62/SQSTM1 binds with claudin-2 to target for selective autophagy in stressed intestinal epithelium |
| title_sort | p62 sqstm1 binds with claudin 2 to target for selective autophagy in stressed intestinal epithelium |
| url | https://doi.org/10.1038/s42003-023-05116-2 |
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