TBC1D1 interacting proteins, VPS13A and VPS13C, regulate GLUT4 homeostasis in C2C12 myotubes
| Autor: | Hadi Al-Hasani, Shosei Kishida, Sharon C. Hook, Alexandra Chadt, Jeremy M. Tavaré, Elaine C. Thomas, Kate J. Heesom |
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| Rok vydání: | 2020 |
| Předmět: |
Male
Proteomics 0301 basic medicine medicine.medical_treatment Muscle Fibers Skeletal Vesicular Transport Proteins lcsh:Medicine Membrane trafficking AMP-Activated Protein Kinases 0302 clinical medicine Homeostasis lcsh:Science Cells Cultured Glucose Transporter Type 4 protein translocation Multidisciplinary diabetes biology Chemistry membrane trafficking GTPase-Activating Proteins Diabetes Cell biology Phosphotyrosine binding Quantitative proteomics Mice Transgenic DNA-binding protein Article 03 medical and health sciences proteomics medicine Animals Humans Protein translocation Insulin lcsh:R Proteins AMPK Phosphoproteins HEK293 Cells 030104 developmental biology Diabetes Mellitus Type 2 biology.protein lcsh:Q Intracellular signalling peptides and proteins Rab Insulin Resistance phosphoproteins 030217 neurology & neurosurgery GLUT4 |
| Zdroj: | Scientific Reports, Vol 10, Iss 1, Pp 1-14 (2020) Hook, S C, Chadt, A, Heesom, K J, Kishida, S, Al-Hasani, H, Tavaré, J M & Thomas, E C 2020, ' TBC1D1 interacting proteins, VPS13A and VPS13C, regulate GLUT4 homeostasis in C2C12 myotubes ', Scientific Reports, vol. 10, 17953 (2020) . https://doi.org/10.1038/s41598-020-74661-1 Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | Proteins involved in the spaciotemporal regulation of GLUT4 trafficking represent potential therapeutic targets for the treatment of insulin resistance and type 2 diabetes. A key regulator of insulin- and exercise-stimulated glucose uptake and GLUT4 trafficking is TBC1D1. This study aimed to identify proteins that regulate GLUT4 trafficking and homeostasis via TBC1D1. Using an unbiased quantitative proteomics approach, we identified proteins that interact with TBC1D1 in C2C12 myotubes including VPS13A and VPS13C, the Rab binding proteins EHBP1L1 and MICAL1, and the calcium pump SERCA1. These proteins associate with TBC1D1 via its phosphotyrosine binding (PTB) domains and their interactions with TBC1D1 were unaffected by AMPK activation, distinguishing them from the AMPK regulated interaction between TBC1D1 and AMPKα1 complexes. Depletion of VPS13A or VPS13C caused a post-transcriptional increase in cellular GLUT4 protein and enhanced cell surface GLUT4 levels in response to AMPK activation. The phenomenon was specific to GLUT4 because other recycling proteins were unaffected. Our results provide further support for a role of the TBC1D1 PTB domains as a scaffold for a range of Rab regulators, and also the VPS13 family of proteins which have been previously linked to fasting glycaemic traits and insulin resistance in genome wide association studies. |
| Databáze: | OpenAIRE |
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