GSK3α phosphorylates dynamin-2 to promote GLUT4 endocytosis in muscle cells.


Journal

The Journal of cell biology
ISSN: 1540-8140
Titre abrégé: J Cell Biol
Pays: United States
ID NLM: 0375356

Informations de publication

Date de publication:
06 02 2023
Historique:
received: 19 02 2021
revised: 17 08 2022
accepted: 31 10 2022
entrez: 29 11 2022
pubmed: 30 11 2022
medline: 2 12 2022
Statut: ppublish

Résumé

Insulin-stimulated translocation of glucose transporter 4 (GLUT4) to plasma membrane of skeletal muscle is critical for postprandial glucose uptake; however, whether the internalization of GLUT4 is also regulated by insulin signaling remains unclear. Here, we discover that the activity of dynamin-2 (Dyn2) in catalyzing GLUT4 endocytosis is negatively regulated by insulin signaling in muscle cells. Mechanistically, the fission activity of Dyn2 is inhibited by binding with the SH3 domain of Bin1. In the absence of insulin, GSK3α phosphorylates Dyn2 to relieve the inhibition of Bin1 and promotes endocytosis. Conversely, insulin signaling inactivates GSK3α and leads to attenuated GLUT4 internalization. Furthermore, the isoform-specific pharmacological inhibition of GSK3α significantly improves insulin sensitivity and glucose tolerance in diet-induced insulin-resistant mice. Together, we identify a new role of GSK3α in insulin-stimulated glucose disposal by regulating Dyn2-mediated GLUT4 endocytosis in muscle cells. These results highlight the isoform-specific function of GSK3α on membrane trafficking and its potential as a therapeutic target for metabolic disorders.

Identifiants

pubmed: 36445308
pii: 213725
doi: 10.1083/jcb.202102119
pmc: PMC9712776
pii:
doi:

Substances chimiques

Adaptor Proteins, Signal Transducing 0
Bin1 protein, mouse 0
Dynamin II EC 3.6.5.5
Glucose IY9XDZ35W2
Glucose Transporter Type 4 0
Glycogen Synthase Kinase 3 EC 2.7.11.26
Insulin 0
Slc2a4 protein, mouse 0
DNM2 protein, mouse EC 3.6.5.5

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

© 2022 Laiman et al.

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Auteurs

Jessica Laiman (J)

Institute of Molecular Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.

Yen-Jung Hsu (YJ)

Institute of Molecular Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.

Julie Loh (J)

Institute of Molecular Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.

Wei-Chun Tang (WC)

ResearchCenter for Applied Sciences, Academia Sinica, Taipei, Taiwan.

Mei-Chun Chuang (MC)

Institute of Molecular Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.

Hui-Kang Liu (HK)

National Research Institute of Chinese Medicine, Ministry of Health and Welfare, Taipei, Taiwan.
Program in the Clinical Drug Development of Herbal Medicine, Taipei Medical University, Taipei, Taiwan.

Wei-Shun Yang (WS)

Division of Nephrology, Department of Internal Medicine, National Taiwan University Hospital, Hsin-Chu Branch, Hsin-Chu, Taiwan.

Bi-Chang Chen (BC)

ResearchCenter for Applied Sciences, Academia Sinica, Taipei, Taiwan.

Lee-Ming Chuang (LM)

Institute of Molecular Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.
Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.

Yi-Cheng Chang (YC)

Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
Institute of Medical Genomics and Proteomics, College of Medicine, National Taiwan University, Taipei, Taiwan.
Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.

Ya-Wen Liu (YW)

Institute of Molecular Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.
Center of Precision Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.

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