Binding of the protein ICln to α-integrin contributes to the activation of ICl current.

ICl is the chloride current induced by cell swelling， and plays a fundamental role in several biological processes， including the regulatory volume decrease (RVD). ICln is a highly conserved， ubiquitously expressed and multifunctional protein involved in the activation of ICl. In platelets， ICln binds to the intracellular domain of the integrin αIIb chain， however， whether the ICln/integrin interaction plays a role in RVD is not known. Here we show that a direct molecular interaction between ICln and the integrin α-chain is not restricted to platelets and involves highly conserved amino acid motifs. Integrin α recruits ICln to the plasma membrane， thereby facilitating the activation of ICl during hypotonicity. Perturbation of the ICln/integrin interaction prevents the transposition of ICln towards the cell surface and， in parallel， impedes the activation of ICl. We suggest that the ICln/integrin interaction interface may represent a new molecular target enabling specific ICl suppression in pathological conditions when this current is deregulated or plays a detrimental role.