Research Project
Full description Recycling of internalised receptors from endosomal compartments is essential for their cell surface homeostasis. Sorting nexin 27 (SNX27) cooperates with the retromer complex in the recycling of proteins containing type I PSD95/Dlg/ZO1 (PDZ) binding motifs. Here we define specific acidic amino acid sequences upstream of the PDZ motif required for high affinity engagement of the SNX27 PDZ domain. However, a subset of SNX27 ligands such as the β2-adrenergic and N-methyl-D-aspartate (NMDA) receptors lack these sequence determinants. Instead we identify conserved sites of phosphorylation that substitute for acidic residues to dramatically enhance SNX27 interactions. This newly identified mechanism points to a likely regulatory switch for PDZ interaction and protein transport by SNX27-retromer. Defining this SNX27-binding code has allowed us to classify more than four hundred potential SNX27 ligands with broad functional implications in signal transduction, neuronal plasticity and metabolite transport.