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Prof G Banting
Applications accepted all year round
About the Project
Tetherin is an integral membrane protein with an unusual topology. It has both a conventional transmembrane domain and a C-terminal glycosylphosphatidylinositol (GPI) anchor [1]. Tetherin exists as a dimer, with disulphide bonds stabilising a parallel coiled coil that links the two membrane anchors. It is present at the cell surface and in an intracellular pool, being internalised from the cell surface via a clathrin-dependent mechanism before delivery back to the cell surface [2]; it also interacts with the actin cytoskeleton [3]. Tetherin is present in sphingolipid and cholesterol rich regions microdomains of the plasma membrane, with this localisation being dependent upon its GPI anchor [1]. Tetherin is so-called because it restricts the release of newly formed HIV virions by tethering them at the surface of infected cells [4]. It has subsequently been shown to restrict the release of a range of different enveloped viruses and to play a role in organising membrane microdomains in mammalian cells [5}. Tetherin has also been implicated in a range of other cellular processes, from regulating the growth and development of B cells through activation of NFkB and MAPK pathways to being implicated in cell adhesion and cell migration as well as metastasis to bone in breast cancer.
The aim of this project is to investigate the role played by tetherin in cell adhesion and cell migration. We have preliminary data (from cells expressing elevated levels of tetherin, from wild type cells and from cells in which tetherin expression has been knocked down using siRNA) that the level of tetherin expression correlates with how tightly cells are attached to the surface on which they are being cultured (plastic or defined extracellular matrix material). This project will use a range of quantitative cell imaging and molecular cell biology techniques to build upon this observation and will provide insights into how tetherin is implicated in metastasis to bone in breast cancer.
Webpage: http://www.bch.bris.ac.uk/staff/gb.html
The aim of this project is to investigate the role played by tetherin in cell adhesion and cell migration. We have preliminary data (from cells expressing elevated levels of tetherin, from wild type cells and from cells in which tetherin expression has been knocked down using siRNA) that the level of tetherin expression correlates with how tightly cells are attached to the surface on which they are being cultured (plastic or defined extracellular matrix material). This project will use a range of quantitative cell imaging and molecular cell biology techniques to build upon this observation and will provide insights into how tetherin is implicated in metastasis to bone in breast cancer.
Webpage: http://www.bch.bris.ac.uk/staff/gb.html
References
1. Kupzig, S., et al., BST-2/HM1.24 is a raft-associated apical membrane protein with an unusual topology. Traffic, 2003. 4: p. 694-709
2. Rollason, R., et al., Clathrin-mediated endocytosis of a lipid-raft-associated protein is mediated through a dual tyrosine motif. J. Cell Sci., 2007. 120(Pt 21): p. 3850 - 3858
3. Rollason, R., et al., A CD317/tetherin-RICH2 complex plays a critical role in the organization of the subapical actin cytoskeleton in polarized epithelial cells. J. Cell Biol., 2009. 184(5): p. 721-736
4. Neil, S.J., T. Zang, and P.D. Bieniasz, Tetherin inhibits retrovirus release and is antagonized by HIV-1 Vpu. Nature, 2008. 451(7177): p. 425-430
5. Billcliff, P.G., Rollason, R., Prior, I., Owen, D.M, Gaus, K. and Banting G. CD317/Tetherin is an Organiser of Membrane Microdomains. Journal of Cell Science, 2013. 126: p. 1553-1564
2. Rollason, R., et al., Clathrin-mediated endocytosis of a lipid-raft-associated protein is mediated through a dual tyrosine motif. J. Cell Sci., 2007. 120(Pt 21): p. 3850 - 3858
3. Rollason, R., et al., A CD317/tetherin-RICH2 complex plays a critical role in the organization of the subapical actin cytoskeleton in polarized epithelial cells. J. Cell Biol., 2009. 184(5): p. 721-736
4. Neil, S.J., T. Zang, and P.D. Bieniasz, Tetherin inhibits retrovirus release and is antagonized by HIV-1 Vpu. Nature, 2008. 451(7177): p. 425-430
5. Billcliff, P.G., Rollason, R., Prior, I., Owen, D.M, Gaus, K. and Banting G. CD317/Tetherin is an Organiser of Membrane Microdomains. Journal of Cell Science, 2013. 126: p. 1553-1564
