| First Author | Mohanan V | Year | 2018 |
| Journal | Science | Volume | 359 |
| Issue | 6380 | Pages | 1161-1166 |
| PubMed ID | 29420262 | Mgi Jnum | J:257317 |
| Mgi Id | MGI:6119883 | Doi | 10.1126/science.aan0814 |
| Citation | Mohanan V, et al. (2018) C1orf106 is a colitis risk gene that regulates stability of epithelial adherens junctions. Science 359(6380):1161-1166 |
| abstractText | Polymorphisms in C1orf106 are associated with increased risk of inflammatory bowel disease (IBD). However, the function of C1orf106 and the consequences of disease-associated polymorphisms are unknown. Here we demonstrate that C1orf106 regulates adherens junction stability by regulating the degradation of cytohesin-1, a guanine nucleotide exchange factor that controls activation of ARF6. By limiting cytohesin-1-dependent ARF6 activation, C1orf106 stabilizes adherens junctions. Consistent with this model, C1orf106(-/-) mice exhibit defects in the intestinal epithelial cell barrier, a phenotype observed in IBD patients that confers increased susceptibility to intestinal pathogens. Furthermore, the IBD risk variant increases C1orf106 ubiquitination and turnover with consequent functional impairments. These findings delineate a mechanism by which a genetic polymorphism fine-tunes intestinal epithelial barrier integrity and elucidate a fundamental mechanism of cellular junctional control. |
