Location

Philadelphia Campus

Start Date

1-5-2013 2:00 PM

End Date

1-5-2013 4:00 PM

Description

Integrin signaling plays important roles in numerous biological processes including maintenance of normal cellular function and essential homeostasis. In addition, integrin signaling is also involved in the metastasis of cancer cells by changes in normal cell adhesion and migration regulation. Studies have shown that Rap1-interacting adaptor molecule (RIAM), an MRL-family protein, recruits the cytoskeletal protein talin to the plasma membrane, thereby mediating the inside-out integrin signaling. The R8 domain of talin has been identified as the RIAM binding site. Recent knock-out studies have shown that talin does not translocate to the plasma membrane without RIAM recruitment. The goal of this project is to elucidate the mechanism of the interaction between the talin R8 domain and RIAM’s talin-binding (TB) region via structural and molecular studies. We will first determine the structure of the RIAM(TB):talin(R8) complex by X-ray crystallography, then perform functional studies in integrin-mediated cell adhesion. Exposing the structural properties of such an interaction is necessary in understanding the mechanism of integrin activation, and will facilitate the development of anticancer compounds.

Included in

Life Sciences Commons

COinS
 
May 1st, 2:00 PM May 1st, 4:00 PM

Mapping the Interaction of Talin:RIAM Complex in Inside-Out Integrin Activation Pathway

Philadelphia Campus

Integrin signaling plays important roles in numerous biological processes including maintenance of normal cellular function and essential homeostasis. In addition, integrin signaling is also involved in the metastasis of cancer cells by changes in normal cell adhesion and migration regulation. Studies have shown that Rap1-interacting adaptor molecule (RIAM), an MRL-family protein, recruits the cytoskeletal protein talin to the plasma membrane, thereby mediating the inside-out integrin signaling. The R8 domain of talin has been identified as the RIAM binding site. Recent knock-out studies have shown that talin does not translocate to the plasma membrane without RIAM recruitment. The goal of this project is to elucidate the mechanism of the interaction between the talin R8 domain and RIAM’s talin-binding (TB) region via structural and molecular studies. We will first determine the structure of the RIAM(TB):talin(R8) complex by X-ray crystallography, then perform functional studies in integrin-mediated cell adhesion. Exposing the structural properties of such an interaction is necessary in understanding the mechanism of integrin activation, and will facilitate the development of anticancer compounds.