Scripps Research Joint Appointments

Faculty, Kellogg School of Science and Technology

Research Focus

Cell migration and morphogenesis relies on the cell’s ability to form specific contacts with its neighbors (adherens junctions) or with the extracellular matrix (focal adhesions). Focal adhesions are directed by integrin receptors, which are unique in provoking both outside-in and inside-out signaling pathways. Integrin receptor activation triggers the rapid reorganization of the actin cytoskeleton and this relies on the function of talin and vinculin, which were thought to simply act as scaffolds that bridge integrin receptors to the actin cytoskeleton. We have taken structural, biochemical, and biological approaches to determine the roles of talin and vinculin. Surprisingly, our studies have revealed that these proteins function as direct signaling effectors that, by undergoing dramatic changes in their structures, transmit the outside-in signal.

Education

B.S., University of Basel, 1988
M.S., University of Basel, 1990
Ph.D., The University of Melbourne, 1994

Selected References

Izard T*, Tran Van Nhieu G, Bois PR. Shigella applies molecular mimicry to subvert vinculin and invade host cells. Journal of Cell Biology, 175:465-475, 2006.

Bois PR, O'Hara BP, Nietlispach D, Kirkpatrick J, Izard T*, The vinculin binding sites of talin and α-actinin are sufficient to activate vinculin. Journal of Biological Chemistry, 281:7228-7236, 2006.

Izard T*, Vonrhein C (2004). Structural basis for amplifying vinculin activation by talin. Journal of Biological Chemistry, 279:27667-27678.

Izard T*, Evans G, Borgon RA, Rush CL, Bricogne G, Bois PRJ (2004). Vinculin activation by talin through helical bundle conversion. Nature, 427:171-175.