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
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