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Title: GNIP1 E3 ubiquitin ligase is a novel player in regulating glycogen metabolism in skeletal muscle.
Author: Montori Grau, Marta
Pedreira-Casahuga, Robert
Boyer-Díaz, Zoé
Lassot, Irena
García Martínez, Celia
Orozco, Anna
Cebrià, Judith
Osorio Conles, Óscar
Chacón, Matilde R.
Vendrell, Joan
Vázquez Carrera, Manuel
Desagher, Solange
Jiménez Chillarón, José Carlos
Gómez Foix, Anna Maria
Keywords: Glicogen
Múscul estriat
Proteïnes portadores
Cèl·lules musculars
Ratolins (Animals de laboratori)
Striated muscle
Carrier proteins
Muscle cells
Mice (Laboratory animals)
Issue Date: 18-Feb-2018
Publisher: W.B. Saunders
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.
Note: Versió postprint del document publicat a:
It is part of: Metabolism-Clinical and Experimental, 2018, vol. 83, p. 177-187
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ISSN: 0026-0495
Appears in Collections:Articles publicats en revistes (Patologia i Terapèutica Experimental)
Articles publicats en revistes (Institut de Biomedicina (IBUB))
Articles publicats en revistes (Farmacologia, Toxicologia i Química Terapèutica)

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