SNX27, a protein of the retromer complex, regulates GPR17 recycling and the kinetics of oligodendrocyte differentiation

The protein transport machineries of cells ensure that the right amount of protein is present at the right time and place. Aberrant protein localization may affect different cellular process including differentiation. Here we reported the role of SNX27, a protein of the endosomal retromer complex, in oligodendrocyte (OL) differentiation. OL maturation is modulated by many factors, including the G protein-coupled receptor 17. Complete maturation of pre-myelinating OL occurs after GPR17 downregulation via still unknown mechanisms. We have previously demonstrated that after internalization GPR17 is sorted into recycling endosome or lysosomes suggesting that balance between recycling/degradation may play a crucial role in GPR17 stability/expression and OPC differentiation. Our data demonstrate that SNX27 plays a crucial role in the plasma membrane recycling of GPR17 via a direct binding with GPR17. Moreover SNX27 knockdown leads to an increased degradation of GPR17 and, more importantly, alters OPC differentiation that enter the myelinating phase precociously. These data highlight the crucial role of SNX27 in the plasma membrane recycling of GPR17 and oligodendrocyte differentiation.