[Role of protein disulfide isomerase in activation of integrins]

Postepy Hig Med Dosw (Online). 2014 May 30:68:666-83. doi: 10.5604/17322693.1105766.
[Article in Polish]

Abstract

Integrins belong to a large family of transmembrane cell adhesion receptors that communicate biochemical and mechanical signals in a bidirectional manner across the plasma membrane. Integrins and their ligands play a crucial role in a number of physiological and pathological processes, including cell migration, cell differentiation, hemostasis, adhesion, angiogenesis, cancer, cell invasiveness and wound healing. Intracellular signals switch integrins into a ligand-competent state as a result of conformational changes within the integrin molecule. Binding of extracellular ligands induces structural changes that can transmit signals to the cell interior. Transition of integrins from an inactive to a ligand binding state involves rearrangement of the disulfide bonding pattern. The rearrangement of disulfide bonds is modulated by protein disulfide isomerase (PDI). PDI has been found on the surface of several types of cells, including endothelial cells, hepatocytes, cancer cells, pancreatic cells and B cells. PDI was identified on the platelet surface, where it plays an important role in platelet reactions such as adhesion, aggregation and secretion. PDI was found to directly interact with integrins. Disulfide-thiol exchange mediated by PDI appears to be involved in the conformational changes in integrin activation. In this report we describe the structure of integrin and the role of disulfide bond rearrangement in its activation.

Publication types

  • Review

MeSH terms

  • Activation, Metabolic / physiology
  • Animals
  • Blood Platelets / metabolism*
  • Cell Adhesion
  • Cell Aggregation / physiology
  • Cell Membrane / metabolism
  • Humans
  • Integrins / chemistry
  • Integrins / metabolism*
  • Ligands
  • Molecular Conformation
  • Protein Disulfide-Isomerases / metabolism*

Substances

  • Integrins
  • Ligands
  • Protein Disulfide-Isomerases