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

    11 Citations (Scopus)

    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

    Bibliographical note

    Funding Information:
    We thank all members of our laboratory for their supports and intellectual inputs during the preparation of this manuscript and Dr. Ki Hoon Jung at Dongguk University Hospital for human liver specimens. Funding: This work was supported by grants from the National Research Foundation of Korea awarded to; Y.-G. Ko (2015R1A5A1009024), H. Lee (2017R1A6A3A01009334) and S. Lee (2017R1D1A1A02017979), and partially by grant from Korea University to Y.-G. Ko and H. Lee.

    Funding Information:
    We thank all members of our laboratory for their supports and intellectual inputs during the preparation of this manuscript and Dr. Ki Hoon Jung at Dongguk University Hospital for human liver specimens. Funding: This work was supported by grants from the National Research Foundation of Korea awarded to; Y.‐G. Ko (2015R1A5A1009024), H. Lee (2017R1A6A3A01009334) and S. Lee (2017R1D1A1A02017979), and partially by grant from Korea University to Y.‐G. Ko and H. Lee.

    Publisher Copyright:
    © 2020 The Authors.

    Keywords

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

    ASJC Scopus subject areas

    • Biochemistry
    • Molecular Biology
    • Genetics

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