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

• Published in: Scientific reports 2019-08, Vol.9 (1), p.1-16, Article 12195
• Main Authors: Schedlbauer, Andreas, Tamma, Grazia, Rodighiero, Simona, Civello, Davide Antonio, Tamplenizza, Margherita, Ledolter, Karin, Nofziger, Charity, Patsch, Wolfgang, Konrat, Robert, Paulmichl, Markus, Dossena, Silvia
• Format: Article
• Language: English
• Subjects: 13; 13/109; 14; 14/33; 631/1647/2204/1453/1970; 631/45/475/2290; 82/6; 9/74; Amino acids; Cell size; Cell surface; Chloride currents; Efficiency; Experiments; Fibroblasts; Humanities and Social Sciences; Hypotonicity; multidisciplinary; Plasma; Platelets; Proteins; Science; Science (multidisciplinary); Transposition
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-019-48496-4

ICl swell 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 swell . 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 swell 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 swell . We suggest that the ICln/integrin interaction interface may represent a new molecular target enabling specific ICl swell suppression in pathological conditions when this current is deregulated or plays a detrimental role.