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Membrane Transport Biology
Kenneth Linton BSc (Hons), PhD
Research field
The Membrane Transport Biology group are interested in the relationship between the structure and function of transport proteins in cellular membranes, and how this relates to human physiology and disease. The three classes of membrane proteins currently under study are the ATP Binding Cassette transporters ABCB1, B4 and B11; the scavenger receptor CD36; and the fatty acid transport proteins or FATPs.
ABCB1, a drug export pump with a high degree of poly-specificity, is an important determinant of barrier function at the cellular and epithelial level and can confer multidrug resistance on cancer cells. The closely related ABCB4 and B11 proteins are expressed in the canalicular membrane of the hepatocyte and are responsible for the transport into bile of lipids and bile acids, respectively; mutations in each cause a range of cholestatic liver diseases. The scavenger receptor CD36 is a polyspecific receptor of, among others, oxidised LDL and thrombospondin and its impairment is implicated in a number of different diseases including atherosclerosis and tumour angiogenesis. FATPs are important for the uptake of long chain fatty acids (lcFA) and implicated in the development of diabetes, but the mechanism of lcFA entry into cells remains unknown.
Using biochemical, structural and cell biological approaches, we aim to develop understanding of the molecular mechanism of each protein. By analysing disease-causing mutations we aim to understand the link between genotype and phenotype, and by characterising their protein:protein interactions at the plasma membrane, we aim to integrate the function of these proteins into the cell biological system.
Key research papers
1 Groen A, Rodriguez Romero M, Kunne C, Dixon PH, Hoosdally, SJ, Wooding C, Williamson C, Seppen J, van den Oever K, Ho-Mok KS, Paulusma CC, Linton KJ and Oude Elferink RPJ. The flippase ATP8B1 counteracts the deleterious function of floppase ABCB4 to maintain hepatocanalicular membrane integrity. J. Clin. Invest. In revision.
2 Hoosdally SJ, Andress EJ, Wooding C, Martin CA and Linton KJ. The human scavenger receptor CD36: glycosylation status and its role in trafficking and function. J. Biol. Chem. (2009) 284, 16277-88.