The role of tetraspanin microdomains in angiogenesis
Angiogenesis is the process of new blood vessel formation from existing vessels. It is important in cancer and heart attack/stroke by providing a supply of blood to solid tumours and atherosclerotic plaques, respectively. Angiogenesis is dependent on the proliferation and migration of the endothelial cells that line all blood vessels. Endothelial cell function is regulated by an array of cell surface receptors, adhesion proteins and signalling molecules. Recently it has emerged that several important cell surface proteins are compartmentalised into tetraspanin-enriched membrane microdomains for optimal function. Tetraspanins are key ‘organisers’ of the cell surface and we have found that endothelial cells express up to 20 of the 33 human tetraspanins. However, most of these tetraspanins remain unstudied.
The proposed work will characterise previously unstudied tetraspanins that we have shown to be expressed by endothelial cells. The aim will be to investigate the role of these tetraspanins in angiogenesis through the generation of new antibodies, proteomic identification of associated proteins, RNAi knockdown in primary human endothelial cells and biological assays to examine endothelial cell function. This work may ultimately lead to new drug targets for the treatment of major diseases such as cancer, heart attack and stroke.
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Bailey RL, Herbert JM, Kabir K, Heath VL, Bicknell R and Tomlinson MG (2011).
The emerging role of tetraspanin microdomains on endothelial cells.
Biochemical Society Transactions. In press.
Rubinstein E, Charrin S and Tomlinson MG.
Organisation of the tetraspanin web.
In Tetraspanins (Berditchevski F and Rubinstein E, eds), Springer. In press.
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.
Biochemical Society Transactions 39:518-523.
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