TBC1D1 Interacting Proteins, VPS13A and VPS13C, Regulate GLUT4 Homeostasis in C2C12 Myotubes

Overview

Journal Sci Rep

Specialty Science

Date 2020 Oct 22

PMID 33087848

Citations 13

Authors

Sharon C Hook

Alexandra Chadt

Kate J Heesom

Shosei Kishida

Hadi Al-Hasani

Jeremy M Tavare

Elaine C Thomas

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Methylome-proteome integration after late-life voluntary exercise training reveals regulation and target information for improved skeletal muscle health.

Chambers T, Dimet-Wiley A, Keeble A, Haghani A, Lo W, Kang G J Physiol. 2024; 603(1):211-237.

PMID: 39058663 PMC: 11702923. DOI: 10.1113/JP286681.

A randomized translational study on protein- and glucose metabolism in skeletal muscles evaluated by gene-ontology, following preoperative oral carbohydrate loading compared to overnight peripheral parenteral nutrition (PPN) before major cancer....

Iresjo B, Smedh U, Engstrom C, Persson J, Martensson C, Lundholm K J Transl Med. 2024; 22(1):675.

PMID: 39039509 PMC: 11265369. DOI: 10.1186/s12967-024-05484-1.

A Pilot Study on the Proteomics Profile of Serum Exosome-Enriched Extracellular Vesicles from Normal versus Individuals with Obesity-Related Insulin Resistance.

Saraswathi V, Ai W, Kumar V, Sharma K, Gopal T, Kumar N Biomedicines. 2024; 12(4).

PMID: 38672154 PMC: 11048419. DOI: 10.3390/biomedicines12040799.

Stevioside Ameliorates Palmitic Acid-Induced Abnormal Glucose Uptake via the PDK4/AMPK/TBC1D1 Pathway in C2C12 Myotubes.

Zhang C, Li S, Li L, Wang R, Luo S, Li G Endocrinol Diabetes Metab. 2024; 7(3):e00482.

PMID: 38556697 PMC: 10982459. DOI: 10.1002/edm2.482.

Novel prognostic biomarker TBC1D1 is associated with immunotherapy resistance in gliomas.

Song D, Yang Q, Li L, Wei Y, Zhang C, Du H Front Immunol. 2024; 15:1372113.

PMID: 38529286 PMC: 10961388. DOI: 10.3389/fimmu.2024.1372113.

References

Sylow L, Kleinert M, Richter E, Jensen T . Exercise-stimulated glucose uptake - regulation and implications for glycaemic control. Nat Rev Endocrinol. 2016; 13(3):133-148. DOI: 10.1038/nrendo.2016.162. View

Hargett S, Walker N, Keller S . Rab GAPs AS160 and Tbc1d1 play nonredundant roles in the regulation of glucose and energy homeostasis in mice. Am J Physiol Endocrinol Metab. 2015; 310(4):E276-88. PMC: 4888528. DOI: 10.1152/ajpendo.00342.2015. View

Guo Y, Qiu H, Xiao S, Wu Z, Yang M, Yang J . A genome-wide association study identifies genomic loci associated with backfat thickness, carcass weight, and body weight in two commercial pig populations. J Appl Genet. 2017; 58(4):499-508. DOI: 10.1007/s13353-017-0405-6. View

Steinberg F, Gallon M, Winfield M, Thomas E, Bell A, Heesom K . A global analysis of SNX27-retromer assembly and cargo specificity reveals a function in glucose and metal ion transport. Nat Cell Biol. 2013; 15(5):461-71. PMC: 4052425. DOI: 10.1038/ncb2721. View

Garvey W, Maianu L, Zhu J, Wallace P, Baron A . Evidence for defects in the trafficking and translocation of GLUT4 glucose transporters in skeletal muscle as a cause of human insulin resistance. J Clin Invest. 1998; 101(11):2377-86. PMC: 508827. DOI: 10.1172/JCI1557. View

Bean B, Dziurdzik S, Kolehmainen K, Fowler C, Kwong W, Grad L . Competitive organelle-specific adaptors recruit Vps13 to membrane contact sites. J Cell Biol. 2018; 217(10):3593-3607. PMC: 6168272. DOI: 10.1083/jcb.201804111. View

Nedachi T, Fujita H, Kanzaki M . Contractile C2C12 myotube model for studying exercise-inducible responses in skeletal muscle. Am J Physiol Endocrinol Metab. 2008; 295(5):E1191-204. DOI: 10.1152/ajpendo.90280.2008. View

Scott R, Lagou V, Welch R, Wheeler E, Montasser M, Luan J . Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways. Nat Genet. 2012; 44(9):991-1005. PMC: 3433394. DOI: 10.1038/ng.2385. View

Fontanesi L, Colombo M, Tognazzi L, Scotti E, Buttazzoni L, DallOlio S . The porcine TBC1D1 gene: mapping, SNP identification, and association study with meat, carcass and production traits in Italian heavy pigs. Mol Biol Rep. 2010; 38(2):1425-31. DOI: 10.1007/s11033-010-0247-3. View

10.

Lesage S, Drouet V, Majounie E, Deramecourt V, Jacoupy M, Nicolas A . Loss of VPS13C Function in Autosomal-Recessive Parkinsonism Causes Mitochondrial Dysfunction and Increases PINK1/Parkin-Dependent Mitophagy. Am J Hum Genet. 2016; 98(3):500-513. PMC: 4800038. DOI: 10.1016/j.ajhg.2016.01.014. View

11.

Grarup N, Overvad M, Sparso T, Witte D, Pisinger C, Jorgensen T . The diabetogenic VPS13C/C2CD4A/C2CD4B rs7172432 variant impairs glucose-stimulated insulin response in 5,722 non-diabetic Danish individuals. Diabetologia. 2011; 54(4):789-94. DOI: 10.1007/s00125-010-2031-2. View

12.

Hatakeyama H, Kanzaki M . Regulatory mode shift of Tbc1d1 is required for acquisition of insulin-responsive GLUT4-trafficking activity. Mol Biol Cell. 2013; 24(6):809-17. PMC: 3596251. DOI: 10.1091/mbc.E12-10-0725. View

13.

Fox C, Heard-Costa N, Cupples L, Dupuis J, Vasan R, Atwood L . Genome-wide association to body mass index and waist circumference: the Framingham Heart Study 100K project. BMC Med Genet. 2007; 8 Suppl 1:S18. PMC: 1995618. DOI: 10.1186/1471-2350-8-S1-S18. View

14.

Cartee G, Funai K . Exercise and insulin: Convergence or divergence at AS160 and TBC1D1?. Exerc Sport Sci Rev. 2009; 37(4):188-95. PMC: 2789346. DOI: 10.1097/JES.0b013e3181b7b7c5. View

15.

Koumanov F, Richardson J, Murrow B, Holman G . AS160 phosphotyrosine-binding domain constructs inhibit insulin-stimulated GLUT4 vesicle fusion with the plasma membrane. J Biol Chem. 2011; 286(19):16574-82. PMC: 3089500. DOI: 10.1074/jbc.M111.226092. View

16.

Yang J, Holman G . Comparison of GLUT4 and GLUT1 subcellular trafficking in basal and insulin-stimulated 3T3-L1 cells. J Biol Chem. 1993; 268(7):4600-3. View

17.

Zhou Z, Menzel F, Benninghoff T, Chadt A, Du C, Holman G . Rab28 is a TBC1D1/TBC1D4 substrate involved in GLUT4 trafficking. FEBS Lett. 2016; 591(1):88-96. DOI: 10.1002/1873-3468.12509. View

18.

Volckmar A, Han C, Putter C, Haas S, Vogel C, Knoll N . Analysis of Genes Involved in Body Weight Regulation by Targeted Re-Sequencing. PLoS One. 2016; 11(2):e0147904. PMC: 4734691. DOI: 10.1371/journal.pone.0147904. View

19.

Degasperi A, Birtwistle M, Volinsky N, Rauch J, Kolch W, Kholodenko B . Evaluating strategies to normalise biological replicates of Western blot data. PLoS One. 2014; 9(1):e87293. PMC: 3903630. DOI: 10.1371/journal.pone.0087293. View

20.

Honisch S, Fehrenbacher B, Lebedeva A, Alesutan I, Castor T, Alkahtani S . Chorein Sensitive Dopamine Release from Pheochromocytoma (PC12) Cells. Neurosignals. 2015; 23(1):1-10. DOI: 10.1159/000442599. View