| First Author | Lee H | Year | 2020 |
| Journal | EMBO Rep | Volume | 21 |
| Issue | 11 | Pages | e49416 |
| PubMed ID | 33030802 | Mgi Jnum | J:301387 |
| Mgi Id | MGI:6505179 | Doi | 10.15252/embr.201949416 |
| Citation | Lee H, et al. (2020) Prominin-1-Radixin axis controls hepatic gluconeogenesis by regulating PKA activity. EMBO Rep 21(11):e49416 |
| abstractText | Prominin-1 (Prom1) is a major cell surface marker of cancer stem cells, but its physiological functions in the liver have not been elucidated. We analyzed the levels of mRNA transcripts in serum-starved primary WT (Prom1(+/+) ) and KO (Prom1(-/-) ) mouse hepatocytes using RNA sequencing (RNA-seq) data, and found that CREB target genes were downregulated. This initial observation led us to determine that Prom1 deficiency inhibited cAMP response element-binding protein (CREB) activation and gluconeogenesis, but not cyclic AMP (cAMP) accumulation, in glucagon-, epinephrine-, or forskolin-treated liver tissues and primary hepatocytes, and mitigated glucagon-induced hyperglycemia. Because Prom1 interacted with radixin, Prom1 deficiency prevented radixin from localizing to the plasma membrane. Moreover, systemic adenoviral knockdown of radixin inhibited CREB activation and gluconeogenesis in glucagon-treated liver tissues and primary hepatocytes, and mitigated glucagon-elicited hyperglycemia. Based on these results, we conclude that Prom1 regulates hepatic PKA signaling via radixin functioning as an A kinase-anchored protein (AKAP). |
