5ema

Publication Abstract from PubMed

Recycling of internalized receptors from endosomal compartments is essential for the receptors' 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-binding motif required for high-affinity engagement of the human SNX27 PDZ domain. However, a subset of SNX27 ligands, such as the beta2 adrenergic receptor and N-methyl-D-aspartate (NMDA) receptor, lack these sequence determinants. Instead, we identified conserved sites of phosphorylation that substitute for acidic residues and dramatically enhance SNX27 interactions. This newly identified mechanism suggests a likely regulatory switch for PDZ interaction and protein transport by the SNX27-retromer complex. Defining this SNX27 binding code allowed us to classify more than 400 potential SNX27 ligands with broad functional implications in signal transduction, neuronal plasticity and metabolite transport.

A molecular code for endosomal recycling of phosphorylated cargos by the SNX27-retromer complex.,Clairfeuille T, Mas C, Chan AS, Yang Z, Tello-Lafoz M, Chandra M, Widagdo J, Kerr MC, Paul B, Merida I, Teasdale RD, Pavlos NJ, Anggono V, Collins BM Nat Struct Mol Biol. 2016 Sep 5. doi: 10.1038/nsmb.3290. PMID:27595347^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.