Complementing pathogens or structural insights into pathogen evasion of the complement system
Year: 2005
Type: article
Abstract: The integrin family of cell adhesion molecules provide a mechanical link between the extracellular matrix (ECM) and the cytoskeleton, and form the nuclei of structural and signaling complexes that regulate cell migration, proliferation and survival, typically in concert with receptors for soluble ligands.Integrins are initially activated by intracellular ("inside-out") signals; following ligation to the ECM, "outside-in" signals lead to reorganization of the cytoskeleton and activation of intracellular signal transduction pathways.Recent studies have demonstrated a critical role for the cytoskeletal protein talin, which binds to the integrin subunit cytoplasmic tail, disrupting tail association and promoting a conformational change in the extracellular domains that leads to enhanced affinity for ECM proteins, and the subsequent clustering of integrins on the cell surface.So what activates talin?Recent evidence points to a prominent role for the enzyme, phosphatidylinositol phosphate kinase type 1-(PIPKI ), which forms complexes with both Src and talin at focal adhesions.PIPKI synthesizes the lipid phosphatidylinositol 4,5 bisphosphate (PtdIns(4,5)P 2 ), a key activator of proteins involved in focal adhesion assembly, including talin and vinculin.Our latest structural studies on integrin, PIPKI , talin and vinculin and their complexes, will be discussed in this context.
Authors: S. M. Lea, P. Roversi, F. Cordes, B. Prosser, S. Johnson
Language: English
Subfield: Immunology and Allergy
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2021137079