GNIP1 E3 ubiquitin ligase is a novel player in regulating glycogen metabolism in skeletal muscle
| العنوان: | GNIP1 E3 ubiquitin ligase is a novel player in regulating glycogen metabolism in skeletal muscle |
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| المؤلفون: | Iréna Lassot, Marta Montori-Grau, Anna M. Gómez-Foix, Manuel Vázquez-Carrera, Anna Orozco, Josep C. Jiménez-Chillarón, Joan Vendrell, Zoe Boyer-Diaz, Solange Desagher, Judith Cebrià, Cèlia García-Martínez, Robert Pedreira-Casahuga, Óscar Osorio-Conles, Matilde R. Chacón |
| المساهمون: | Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM) |
| المصدر: | Dipòsit Digital de la UB Universidad de Barcelona Metabolism Metabolism, Elsevier, 2018, 83, pp.177--187. ⟨10.1016/j.metabol.2018.02.005⟩ |
| بيانات النشر: | W.B. Saunders, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, Glycogenin, Carrier proteins, Physiology, Endocrinology, Diabetes and Metabolism, Muscle Fibers, Skeletal, Muscle cells, Tripartite Motif Proteins, Mice, 0302 clinical medicine, Endocrinology, Ubiquitin, Cèl·lules musculars, Myocyte, Cells, Cultured, biology, Myogenesis, Chemistry, Cardiac muscle, Metabolisme, Ubiquitin ligase, Cell biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Glycogen, medicine.medical_specialty, Proteïnes portadores, Ratolins (Animals de laboratori), Ubiquitin-Protein Ligases, Striated muscle, GNIP1: TRIM7 isoform 1 Glycogen metabolism Skeletal muscle TRIM7: TRIM7 isoform 4, Fisiologia, 03 medical and health sciences, Internal medicine, medicine, Animals, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Muscle, Skeletal, Glycogen synthase, Skeletal muscle, Glicogen, HEK293 Cells, 030104 developmental biology, Metabolism, Mice (Laboratory animals), biology.protein, Múscul estriat, Carrier Proteins |
| الوصف: | International audience; 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-3alpha/beta (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. |
| وصف الملف: | application/pdf |
| تدمد: | 0026-0495 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::17afa1794ef6fd85be22cc35447d460eTest http://hdl.handle.net/2445/164917Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....17afa1794ef6fd85be22cc35447d460e |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 00260495 |
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