| First Author | Fan S | Year | 2022 |
| Journal | iScience | Volume | 25 |
| Issue | 5 | Pages | 104316 |
| PubMed ID | 35602956 | Mgi Jnum | J:325128 |
| Mgi Id | MGI:7283701 | Doi | 10.1016/j.isci.2022.104316 |
| Citation | Fan S, et al. (2022) JAM-A signals through the Hippo pathway to regulate intestinal epithelial proliferation. iScience 25(5):104316 |
| abstractText | JAM-A is a tight-junction-associated protein that contributes to regulation of intestinal homeostasis. We report that JAM-A interacts with NF2 and LATS1, functioning as an initiator of the Hippo signaling pathway, well-known for regulation of proliferation. Consistent with these findings, we observed increased YAP activity in JAM-A-deficient intestinal epithelial cells (IEC). Furthermore, overexpression of a dimerization-deficient mutant, JAM-A-DL1, failed to initiate Hippo signaling, phenocopying JAM-A-deficient IEC, whereas overexpression of JAM-A-WT activated Hippo signaling and suppressed proliferation. Lastly, we identify EVI1, a transcription factor reported to promote cellular proliferation, as a contributor to the pro-proliferative phenotype in JAM-A-DL1 overexpressing IEC downstream of YAP. Collectively, our findings establish a new role for JAM-A as a cell-cell contact sensor, raising implications for understanding the contribution(s) of JAM-A to IEC proliferation in the mammalian epithelium. |
