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Molecular Components of Intracellular Membrane Traffic

Research Groupings: Structural and molecular cell biology | Developmental and regenerative biology and medicine

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 invaginate and pinch off to form clathrin-coated vesicles that subsequently deliver their cargo to further intracellular compartments.

A virus caught in the act of entering a cell via a clathrin-coated pit (electron micrograph by A.P. Jackson and D. Hill).

We are interested in the function of individual components of this system. We have used a chicken B cell-line that has an unusually high rate of homologous recombination to knock out the clathrin gene and study the functional consequences in a vertebrate context. Our results have uncovered an unexpected connection between clathrin-mediated pathways and survival factor signalling.

Predicted structural model for the extracellular domain of the b3 subunit.

Function of sodium channel auxiliary subunits in the intracellular trafficking of the channel
The voltage-gated sodium channel is localized to the neuronal plasma membrane and plays a vital role in propagating the neuronal action potential. It consists of a central alpha subunit together with two auxiliary subunits named beta 1 and beta 2. We have recently identified a third such subunit beta 3, which may be preferentially associated with some alpha subunit types. The beta subunits modulate the kinetic properties of the alpha subunit but also enhance the efficiency with which mature channels assemble and are processed through the secretory pathway. We are currently examining the role of beta 3 in this latter process using cell-transfections, GFP-tagging of wild-type and mutated versions of the molecule.

Lab members
Fiona Cusdin, Petra Staubitz

References