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Accepted version

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2018-02-18

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cc-by-nc-nd (c) W.B. Saunders, 2018
Please use this identifier to cite or link to this item: https://hdl.handle.net/2445/164917

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

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https://doi.org/10.1016/j.metabol.2018.02.005

Abstract

Background: 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. Objectives: 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. Results: 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 modifications led to decreased blood glucose levels, lactate levels and body weight, without changing whole-body insulin or glucose tolerance in mouse. Conclusion: GNIP1 is an ubiquitin ligase with a markedly glycogenic effect in skeletal muscle.

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Glicogen, Fisiologia, Metabolisme, Múscul estriat, Proteïnes portadores, Cèl·lules musculars, Ratolins (Animals de laboratori)

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Glycogen, Physiology, Metabolism, Striated muscle, Carrier proteins, Muscle cells, Mice (Laboratory animals)

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Articles publicats en revistes (Farmacologia, Toxicologia i Química Terapèutica)
Articles publicats en revistes (Institut de Biomedicina (IBUB))
Articles publicats en revistes (Patologia i Terapèutica Experimental)

Citation

MONTORI GRAU, Marta, et al. GNIP1 E3 ubiquitin ligase is a novel player in regulating glycogen metabolism in skeletal muscle. Metabolism-Clinical and Experimental. 2018. Vol. 83, num. 177-187. ISSN 0026-0495. [consulted: 14 of August of 2026]. Available at: https://hdl.handle.net/2445/164917

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