PIPKI gamma 90 negatively regulates LFA-1-mediated adhesion and activation in antigen-induced CD4+ T cells.

T cell activation requires the formation and maintenance of stable interactions between T cells and APCs. The formation of stable T cell-APC contacts depends on the activation of the integrin LFA-1 (CD11aCD18). Several positive regulators of LFA-1 activation downstream of proximal TCR signaling have been identified, including talin; however, negative regulators of LFA-1 activity remain largely unexplored.

Calpain 4 is not necessary for LFA-1-mediated function in CD4+ T cells.

Background: T cell activation and immune synapse formation require the appropriate activation and clustering of the integrin, LFA-1. Previous work has reported that the calpain family of calcium-dependent proteases are important regulators of integrin activation and modulate T cell adhesion and migration. However, these studies have been limited by the use of calpain inhibitors, which have known off-target effects.

Adhesions ring: a structural comparison between podosomes and the immune synapse.

Podosomes and the immune synapse are integrin-mediated adhesive structures that share a common ring-like morphology. Both podosomes and immune synapses have a central core surrounded by a peripheral ring containing talin, vinculin and paxillin. Recent progress suggests significant parallels between the regulatory mechanisms that contribute to the formation of these adhesive structures.

Talin1 regulates TCR-mediated LFA-1 function.

The leukocyte integrin LFA-1 plays a critical role in T cell trafficking and T cell adhesion to APCs. It is known that integrin-mediated adhesion is regulated by changes in integrin ligand-binding affinity and valency through inside-out signaling. However, the molecular mechanisms involved in TCR-mediated LFA-1 regulation are not well understood.

The conserved C-terminal I/LWEQ module targets Talin1 to focal adhesions.

The cytoskeletal protein Talin1 is a critical link between integrins and the actin cytoskeleton, where it is required for the structural and signaling functions of integrin-containing adhesion complexes. However, the elements in Talin1 that are responsible for localizing it to adhesion complexes are not known. In this report we have used a series of constructs based on the modular structure of Talin1 to determine the structural elements that specify the subcellular localization of Talin1.

TRPM7 regulates cell adhesion by controlling the calcium-dependent protease calpain.

m-Calpain is a protease implicated in the control of cell adhesion through focal adhesion disassembly. The mechanism by which the enzyme is spatially and temporally controlled is not well understood, particularly because the dependence of calpain on calcium exceeds the submicromolar concentrations normally observed in cells. Here we show that the channel kinase TRPM7 localizes to peripheral adhesion complexes with m-calpain, where it regulates cell adhesion by controlling the activity of the protease.