Sorting nexin 27 couples PTHR trafficking to retromer for signal regulation in osteoblasts during bone growth

• DOI: 10.1091/mbc.e15-12-0851
• Publication Date: 2016-02-25T04:36:32Z
• Authors: Audrey S. M. Chan; Thomas Clairfeuille; Euphemie Landao-B...; Genevieve Kinna; Pei Ying Ng; Li Shen Loo; Tak Sum Cheng; Minghao Zheng; Wanjin Hong; Rohan D. Teasdale; Brett M. Collins; Nathan J. Pavlos
• Keywords: Sorting nexin; Retromer; Internalization

The parathyroid hormone 1 receptor (PTHR) is central to the process of bone formation and remodeling. PTHR signaling requires internalization into endosomes, which then terminated by recycling or degradation. Here we show that sorting nexin 27 (SNX27) functions as an adaptor couples retromer trafficking complex. SNX27 binds directly C-terminal PDZ-binding motif PTHR, wiring it for endosomal sorting. structure bound reveals a high-affinity interface involving conserved electrostatic interactions. Mechanistically, depletion augments intracellular in endosomes. Osteoblasts genetically lacking similar disruptions greatly reduced capacity mineralization, contributing profound skeletal deficits SNX27-knockout mice. Taken together, our data support critical role SNX27-retromer mediated transport normal development.