GNIP1 E3 ubiquitin ligase is a novel player in regulating glycogen metabolism in skeletal muscle

Metabolism: Clinical and Experimental
Marta Montori-GrauAnna Ma Gómez-Foix

Abstract

Glycogenin-interacting protein 1 (GNIP1) is a tripartite motif (TRIM) protein with E3 ubiquitin ligase activity that interacts with glycogenin. These data suggest that GNIP1 could play a major role in the control of glycogen metabolism. However, direct evidence based on functional analysis remains to be obtained. The aim of this study was 1) to define the expression pattern of glycogenin-interacting protein/Tripartite motif containing protein 7 (GNIP/TRIM7) isoforms in humans, 2) to test their ubiquitin E3 ligase activity, and 3) to analyze the functional effects of GNIP1 on muscle glucose/glycogen metabolism both in human cultured cells and in vivo in mice. We show that GNIP1 was the most abundant GNIP/TRIM7 isoform in human skeletal muscle, whereas in cardiac muscle only TRIM7 was expressed. GNIP1 and TRIM7 had autoubiquitination activity in vitro and were localized in the Golgi apparatus and cytosol respectively in LHCN-M2 myoblasts. GNIP1 overexpression increased glucose uptake in LHCN-M2 myotubes. Overexpression of GNIP1 in mouse muscle in vivo increased glycogen content, glycogen synthase (GS) activity and phospho-GSK-3α/β (Ser21/9) and phospho-Akt (Ser473) content, whereas decreased GS phosphorylation in Ser640. These mo...Continue Reading

Citations

Oct 12, 2018·Journal of Virology·Robert C OrchardHerbert W Virgin
Aug 25, 2020·Current Clinical Microbiology Reports·Maria I GiraldoRicardo Rajsbaum
Jul 10, 2020·Nature·Maria I GiraldoRicardo Rajsbaum
Jan 14, 2021·Cell Biology International·Tingting WanYanbo Li
Feb 8, 2021·Genetics, Selection, Evolution : GSE·Wei LiJie Wen

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