| First Author | Tennant BR | Year | 2015 |
| Journal | Mol Endocrinol | Volume | 29 |
| Issue | 9 | Pages | 1254-68 |
| PubMed ID | 26177052 | Mgi Jnum | J:316197 |
| Mgi Id | MGI:6834253 | Doi | 10.1210/ME.2014-1387 |
| Citation | Tennant BR, et al. (2015) Myt3 Mediates Laminin-V/Integrin-beta1-Induced Islet-Cell Migration via Tgfbi. Mol Endocrinol 29(9):1254-68 |
| abstractText | Myt3 is a prosurvival factor in pancreatic islets; however, its role in islet-cell development is not known. Here, we demonstrate that myelin transcription factor 3 (Myt3) is expressed in migrating islet cells in the developing and neonatal pancreas and thus sought to determine whether Myt3 plays a role in this process. Using an ex vivo model of islet-cell migration, we demonstrate that Myt3 suppression significantly inhibits laminin-V/integrin-beta1-dependent alpha- and beta-cell migration onto 804G, and impaired 804G-induced F-actin and E-cadherin redistribution. Exposure of islets to proinflammatory cytokines, which suppress Myt3 expression, had a similar effect, whereas Myt3 overexpression partially rescued the migratory ability of the islet cells. We show that loss of islet-cell migration, due to Myt3 suppression or cytokine exposure, is independent of effects on islet-cell survival or proliferation. Myt3 suppression also had no effect on glucose-induced calcium influx, F-actin remodeling or insulin secretion by beta-cells. RNA-sequencing (RNA-seq) analysis of transduced islets showed that Myt3 suppression results in the up-regulation of Tgfbi, a secreted diabetogenic factor thought to impair cellular adhesion. Exposure of islets to exogenous transforming growth factor beta-induced (Tgfbi) impaired islet-cell migration similar to Myt3 suppression. Taken together, these data suggest a model by which cytokine-induced Myt3 suppression leads to Tgfbi de-repression and subsequently to impaired islet-cell migration, revealing a novel role for Myt3 in regulating islet-cell migration. |
