Sorting Nexin 31 Binds Multiple beta Integrin Cytoplasmic Domains and Regulates beta 1 Integrin Surface Levels and Stability

Trafficking of alpha 5 beta 1 integrin to lysosomes and its subsequent degradation is influenced by ligand occupancy and the binding of SNX17 via its protein 4.1, ezrin, radixin, moesin (FERM) domain to the membrane-distal NPxY motif in the cytoplasmic domain of beta 1 integrin in early endosomes. Two other sorting nexin (SNX) family members, namely SNX27 and SNX31, share with SNX17 next to their obligate phox domain a FERM domain, which may enable them to bind beta integrin tails. Here we report that, in addition to SNX17, SNX31 but not SNX27 binds several beta integrin tails in early endosomes in a PI3 (phosphatidylinositide 3)-kinase-dependent manner. Similarly like SNX17, binding of SNX31 with beta 1 integrin tails in early endosomes occurs between the FERM domain and the membrane-distal NPxY motif in the beta 1 integrin cytoplasmic domain. Furthermore, expression of SNX31 rescues 61 integrin surface levels and stability in SNX17-depleted cells. In contrast to SNX17, expression of SNX31 is restricted and found highly expressed in bladder and melanoma tissue. Altogether, these results demonstrate that SNX31 is an endosomal regulator of beta integrins with a restricted expression pattern. (C) 2014 Elsevier Ltd. All rights reserved