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. 2016 Oct;23(10):921-932.
doi: 10.1038/nsmb.3290. Epub 2016 Sep 5.

A molecular code for endosomal recycling of phosphorylated cargos by the SNX27-retromer complex

Thomas Clairfeuille  1 , Caroline Mas  1 , Audrey S M Chan  2 , Zhe Yang  1 , Maria Tello-Lafoz  3 , Mintu Chandra  1 , Jocelyn Widagdo  4 , Markus C Kerr  1 , Blessy Paul  1 , Isabel Mérida  3 , Rohan D Teasdale  1 , Nathan J Pavlos  2 , Victor Anggono  4 , Brett M Collins  1
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Free article

A molecular code for endosomal recycling of phosphorylated cargos by the SNX27-retromer complex

Thomas Clairfeuille et al. Nat Struct Mol Biol. 2016 Oct.
Free article

Abstract

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 β2 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.

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