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Prominin‐1‐Radixin axis controls hepatic gluconeogenesis by regulating PKA activity
Author(s) -
Lee Hyun,
Yu DongMin,
Park Jun Sub,
Lee Hwayeon,
Kim JunSeok,
Kim Hong Lim,
Koo SeungHoi,
Lee JaeSeon,
Lee Sungsoo,
Ko YoungGyu
Publication year - 2020
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201949416
Subject(s) - creb , radixin , endocrinology , glucagon , medicine , gene knockdown , biology , microbiology and biotechnology , protein kinase a , gluconeogenesis , moesin , kinase , cell , transcription factor , biochemistry , gene , insulin , cytoskeleton , metabolism , ezrin
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).