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Tony Jackson

Molecular components of intracellular membrane traffic

Role of clathrin in membrane traffic: Selected macromolecules such as growth factors and plasma lipoporoteins are internlalised into cells by receptor-mediated endocytosis. The macromolecules bind receptors on the plasma-membrane which become concentrated in specific regions known as clathrin-coated pits. These pits pinch off to form clathrin-coated vesicles that subsequently deliver their cargo to further intracellular compartments.

We use a chicken B cell-line (DT40) that has an unusually high rate of homologous recombination to knock out the clathrin gene and study the consequences in a vertebrate context. We are using a variety of cell biological and proteomic methods to study clathrin function.

Function of sodium channel auxiliary subunits in the intracellular trafficking of the channel: The voltage-gated sodium channel plays a vital role in propagating the neuronal action potential. It consists of an alpha subunit and additional auxiliary beta subunits. We were one of the groups that identified the third such beta subunit. We have recently identified a third subunit 3. The beta subunits affect channel electrophysiological behaviour and help traffic the channel to the plasma membrane. The extracellular region of beta 3 forms an immunoglobulin domain. We are currently examining the role of beta 3 subunit in membrane traffic of the channel and in localizing the channel within the neuronal plasma membrane.

Lab members: Fiona Cusdin, Petra Staubitz

Key publications:

1. Wettey et al., Science 297, 1521 - 1525 (2002)

2. Wettey FR and Jackson AP Chapter 9 in ‘The DT40 Handbook” (eds J.M. Buerstedde & S. Takeda) Springer Publishing House (2006)

3. Hall SL et al., Mol. Cell. Prot. 8 1295 - 1305 (2010)

4. Neumann-Staubitz P, et al., PLoS One. (2010) 5 (8): e12017

5. Morgan, K et al., Proc. Natl. Acad. Sci (USA) 97, 23080 - 2313

6. Cusdin, FS., Clare, JJ., and Jackson, AP Traffic 9 17-26 (2008)

7. Cusdin FS, et al., J Biol Chem 285, 33404 - 12 (2010)

8. Hakim et al., Acta Physiol. 198 47 - 59 (2010)