Research Theme within School of Biosciences: Molecular and Cell Biology
Regulation of platelet and endothelial cell surface receptors by tetraspanin microdomains
Platelets and endothelial cells play essential roles in maintaining blood vessel integrity and in wound healing, but can also give rise to the initiation and progression of atherosclerosis, leading to heart attack and stroke. These cells possess an array of receptors and adhesion molecules that regulate their function in health and disease. The tetraspanins are a superfamily of transmembrane proteins that interact with and 'organise' other cell surface proteins into membrane microdomains, in organisms as diverse as plants, fungi and animals. Such partitioning of proteins into membrane microdomains is critical for processes such as cell signaling and adhesion. By identifying novel tetraspanin-associated proteins and characterizing their regulation within tetraspanin microdomains, Dr Mike Tomlinson hopes to identify new drug targets for the prevention and treatment of cardiovascular disease.
Dr Tomlinson’s studies are heavily focussed on genetically modified platelets and primary endothelial cells, with some additional use of cell line models. The techniques that his group employ include genomics and proteomics, functional assays for platelets and endothelial cells, and analyses of protein-protein interactions through microscopy and biochemical methods.
He is funded by a Senior Fellowship from the British Heart Foundation.
Tomlinson MG (2011). Analysis of the platelet and megakaryocyte transcriptomes using serial analysis of gene expression. In Platelet Proteomics (Garcia A and Senis YA, eds), Wiley, pp. 209-230.
Haining EJ, Yang J and Tomlinson MG (2011). Tetraspanin microdomains: fine-tuning platelet function. Biochem. Soc. Trans. 39: 518-523.
Rubinstein E, Charrin S and Tomlinson MG (2011). Organisation of tetraspanin webs. In Tetraspanins (Berditchevski F and Rubinstein E, eds), Springer. In press.
Hughes CE, Pollitt AY, Mori J, Eble JA, Tomlinson MG, Hartwig JH, O’Callaghan CA, Futterer K and Watson SP (2010). CLEC-2 activates Syk through dimerisation. Blood 115: 2947-2955.
Tomlinson MG (2009). Platelet tetraspanins: small but interesting. J. Thromb. Haemost. 7: 2070-2073.
Senis YA*, Tomlinson MG*, Ellison S, Mazharian A, Lim J, Zhao Y, Kornerup KN, Auger JM, Thomas SG, Dhanjal T, Kalia N, Zhu JW, Weiss A and Watson SP. (2009). The tyrosine phosphatase CD148 is an essential positive regulator of platelet activation and thrombosis. Blood 113: 4942-4954. (*Denotes joint first author).
Protty MB, Watkins NA, Colombo D, Thomas SG, Heath VL, Herbert JMJ, Bicknell R, Senis YA, Ashman LK, Berditchevski F, Ouwehand WH, Watson SP and Tomlinson MG (2009). Identification of Tspan9 as a novel platelet tetraspanin and the collagen receptor GPVI as a component of tetraspanin microdomains. Biochem. J. 417: 391-400.
Mori J, Pearce AC, Spalton JC, Grygielska B, Eble JA, Tomlinson MG, Senis YA and Watson SP. (2008). G6b-B inhibits constitutive and agonist-induced signalling by GPVI and CLEC-2. J. Biol. Chem. 283: 35419-35427.
Tomlinson MG, Calaminus SD, Berlanga O, Auger JM, Bori-Sanz T, Meyaard L and Watson SP (2007). Collagen promotes sustained GPVI signalling in platelets and cell lines. J. Thromb. Haemost. 5: 2274-2283.
Senis YA, Tomlinson MG, Garcia A, Dumon S, Heath VL, Herbert J, Cobbold SP, Spalton JC, Ayman S, Antrobus R, Zitzmann N, Bicknell R, Frampton J, Authi KS, Martin A, Wakelam MJ and Watson SP (2007). A comprehensive proteomics and genomics analysis reveals novel transmembrane proteins in human platelets and mouse megakaryocytes including G6b-B, a novel immunoreceptor tyrosine-based inhibitory motif protein. Mol. Cell. Prot. 6: 548-564.
Fuller GL, Williams JA, Tomlinson MG, Eble JA, Hanna SL, Pohlmann S, Suzuki-Inoue K, Ozaki Y, Watson SP and Pearce AC (2007). The C-type lectin receptors CLEC-2 and Dectin-1, but not DC-SIGN, signal via a novel YXXL-dependent signalling cascade. J. Biol. Chem. 282: 12397-12409.
Berlanga O, Bori-Sanz T, James JR, Frampton J, Davis SJ, Tomlinson MG and Watson SP (2007). GPVI oligomerisation in cell lines and platelets. J. Thromb. Haemost 5: 1026-1033.
Garcia A, Senis Y, Tomlinson MG and Watson SP (2006). Platelet genomics and proteomics. In Platelets (Michelson AD, ed), Academic Press/Elsevier Science, New York, pp. 99-116.