Prominin-1-Radixin axis controls hepatic gluconeogenesis by regulating PKA activity

Hyun Lee, Dong Min Yu, Jun Sub Park, Hwayeon Lee, Jun Seok Kim, Hong Lim Kim, Seung Hoi Koo, Jae Seon Lee, Sungsoo Lee, Young Gyu Ko

Research output: Contribution to journalArticlepeer-review

Abstract

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).

Original languageEnglish
Article numbere49416
JournalEMBO Reports
Volume21
Issue number11
DOIs
Publication statusPublished - 2020 Nov 5

Keywords

  • Prominin-1
  • cAMP signaling
  • gluconeogenesis
  • protein kinase A
  • radixin

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics

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