Dr Peter Taylor
Research
My research (recently funded by The Wellcome Trust, BBSRC and Scottish Government (RESAS)) centres on the mechanisms of amino acid transport across mammalian cell membranes and their physiological functions in health and disease (including malnutrition). My principal focus is the role of the LAT1 (SLC7A5) amino acid transporter in sensing and signalling "availability" of amino acids to intracellular mechanisms (notably the mTORC1 pathway) which regulate protein synthesis, cell size and growth. We have developed a conditional knockout of LAT1 (SLC7A5) in mice to enable these studies. LAT1 also facilitates the actions of thyroid hormones (which are amino acid derivatives) by transporting them into target cells.
Publications
Sinclair, LV, Howden, A, Brenes Murillo, A, Spinelli, L, Hukelmann, J, Macintyre, AN, Liu, X, Thomson, S, Taylor, P, Rathmell, JC, Locasale, JW, Lamond, A & Cantrell, DA 2019, 'Antigen receptor control of methionine metabolism in T cells' eLife, vol. 8, e44210. https://doi.org/10.7554/eLife.44210
Stretton, C, Lipina, C, Hyde, R, Cwiklinski, E, Hoffmann, TM, Taylor, PM & Hundal, HS 2019, 'CDK7 is a component of the integrated stress response regulating SNAT2 (SLC38A2)/System A adaptation in response to cellular amino acid deprivation' Biochimica et Biophysica Acta. Molecular Cell Research, vol. 1866, no. 6, pp. 978-991. https://doi.org/10.1016/j.bbamcr.2019.03.002
Hoffmann, T, Cwiklinski, E, Shah, D, Stretton, C, Hyde, R, Taylor, P & Hundal, H 2018, 'Effects of sodium and amino acid substrate availability upon the expression and stability of the SNAT2 (SLC38A2) amino acid transporter' Frontiers in Pharmacology, vol. 9, 63, pp. 1-9. https://doi.org/10.3389/fphar.2018.00063
Sinclair, L, Neyens, D, Ramsay, G, Taylor, P & Cantrell, D 2018, 'Single cell analysis of kynurenine and System L amino acid transport in T cells' Nature Communications, vol. 9, no. 1, 1981 (2018). https://doi.org/10.1038/s41467-018-04366-7
Millward, DJ, Halliday, D, Hundal, H, Taylor, P, Atherton, P, Greenhaff, P & Smith, K 2017, 'Michael John Rennie, MSc, PhD, FRSE, FHEA, 1946-2017: an appreciation of his work on protein metabolism in human muscle' American Journal of Clinical Nutrition, vol. 106, no. 1, pp. 1-9. https://doi.org/10.3945/ajcn.117.157818
Liu, R., Iadevaia, V., Averous, J., Taylor, P. M., Zhang, Z. and Proud, C. G. (2014) Impairing the production of ribosomal RNA activates mammalian target of rapamycin complex 1 signalling and downstream translation factors. Nucleic acids research. 42, 5083-5096 d.o.i 10.1093/nar/gku130 Pubmed: 4005692 PMC: 24526220
Nardi, F., Hoffmann, T. M., Stretton, C., Cwiklinski, E., Taylor, P. M. and Hundal, H. S. (2015) Proteasomal modulation of cellular SNAT2 (SLC38A2) abundance and function by unsaturated fatty acid availability. The Journal of biological chemistry. 290, 8173-8184 d.o.i 10.1074/jbc.M114.625137 Pubmed: 4375474 PMC: 25653282
Stretton, C., Hoffmann, T. M., Munson, M. J., Prescott, A., Taylor, P. M., Ganley, I. G. and Hundal, H. S. (2015) GSK3-mediated raptor phosphorylation supports amino-acid-dependent mTORC1-directed signalling. The Biochemical journal. 470, 207-221 d.o.i 10.1042/BJ20150404 Pubmed: 4652938 PMC: 26348909
Watson, A., Lipina, C., McArdle, H. J., Taylor, P. M. and Hundal, H. S. (2016) Iron depletion suppresses mTORC1-directed signalling in intestinal Caco-2 cells via induction of REDD1. Cellular signalling. 28, 412-424 d.o.i 10.1016/j.cellsig.2016.01.014 Pubmed: 4804389 PMC: 26827808
Taylor, P. M. (2014) Role of amino acid transporters in amino acid sensing. The American journal of clinical nutrition. 99, 223S-230S d.o.i 10.3945/ajcn.113.070086 Pubmed: 3862456 PMC: 24284439
Poncet, N., Mitchell, F. E., Ibrahim, A. F., McGuire, V. A., English, G., Arthur, J. S., Shi, Y. B. and Taylor, P. M. (2014) The catalytic subunit of the system L1 amino acid transporter (slc7a5) facilitates nutrient signalling in mouse skeletal muscle. PloS one. 9, e89547 d.o.i 10.1371/journal.pone.0089547 Pubmed: 3935884 PMC: 24586861
Sinclair, L. V., Rolf, J., Emslie, E., Shi, Y. B., Taylor, P. M. and Cantrell, D. A. (2013) Control of amino-acid transport by antigen receptors coordinates the metabolic reprogramming essential for T cell differentiation. Nature immunology. 14, 500-508 d.o.i 10.1038/ni.2556 Pubmed: 3672957 PMC: 23525088
Baird, F. E., Bett, K. J., MacLean, C., Tee, A. R., Hundal, H. S. and Taylor, P. M. (2009) Tertiary active transport of amino acids reconstituted by coexpression of System A and L transporters in Xenopus oocytes. American journal of physiology. Endocrinology and metabolism. 297, E822-829 d.o.i 10.1152/ajpendo.00330.2009 PMC: 19622785
Hyde, R., Cwiklinski, E. L., MacAulay, K., Taylor, P. M. and Hundal, H. S. (2007) Distinct sensor pathways in the hierarchical control of SNAT2, a putative amino acid transceptor, by amino acid availability. The Journal of biological chemistry. 282, 19788-19798 d.o.i 10.1074/jbc.M611520200 Pubmed: PMC: 17488712
Cuthbertson, D., Smith, K., Babraj, J., Leese, G., Waddell, T., Atherton, P., Wackerhage, H., Taylor, P. M. and Rennie, M. J. (2005) Anabolic signaling deficits underlie amino acid resistance of wasting, aging muscle. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 19, 422-424 d.o.i 10.1096/fj.04-2640fje PMC: 1559648
Impact
New opportunities for nutritional therapy may lie in targeting transporters such as LAT1 so as to promote anabolic signals designed to retain lean tissue mass in ageing or regain it during rehabilitation from disease or injury. I have been invited to presented these ideas to the American Society of Nutrition:- Online here