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

Chan, Audrey S. M., Clairfeuille, Thomas, Landao-Bassonga, Euphemie, Kinna, Genevieve, Ng, Pei Ying, Loo, Li Shen, Cheng, Tak Sum, Zheng, Minghao, Hong, Wanjin, Teasdale, Rohan D., Collins, Brett M. and Pavlos, Nathan J (2016) Sorting nexin 27 couples PTHR trafficking to retromer for signal regulation in osteoblasts during bone growth. Molecular Biology of the Cell, 27 8: 1367-1382. doi:10.1091/mbc.E15-12-0851


Author Chan, Audrey S. M.
Clairfeuille, Thomas
Landao-Bassonga, Euphemie
Kinna, Genevieve
Ng, Pei Ying
Loo, Li Shen
Cheng, Tak Sum
Zheng, Minghao
Hong, Wanjin
Teasdale, Rohan D.
Collins, Brett M.
Pavlos, Nathan J
Title Sorting nexin 27 couples PTHR trafficking to retromer for signal regulation in osteoblasts during bone growth
Journal name Molecular Biology of the Cell   Check publisher's open access policy
ISSN 1939-4586
1059-1524
Publication date 2016-04-15
Year available 2016
Sub-type Article (original research)
DOI 10.1091/mbc.E15-12-0851
Open Access Status DOI
Volume 27
Issue 8
Start page 1367
End page 1382
Total pages 16
Place of publication Bethesda, MD, United States
Publisher American Society for Cell Biology
Collection year 2017
Language eng
Abstract The parathyroid hormone 1 receptor (PTHR) is central to the process of bone formation and remodeling. PTHR signaling requires receptor internalization into endosomes, which is then terminated by recycling or degradation. Here we show that sorting nexin 27 (SNX27) functions as an adaptor that couples PTHR to the retromer trafficking complex. SNX27 binds directly to the C-terminal PDZ-binding motif of PTHR, wiring it to retromer for endosomal sorting. The structure of SNX27 bound to the PTHR motif reveals a high-affinity interface involving conserved electrostatic interactions. Mechanistically, depletion of SNX27 or retromer augments intracellular PTHR signaling in endosomes. Osteoblasts genetically lacking SNX27 show similar disruptions in PTHR signaling and greatly reduced capacity for bone mineralization, contributing to profound skeletal deficits in SNX27-knockout mice. Taken together, our data support a critical role for SNX27-retromer mediated transport of PTHR in normal bone development.
Keyword Parathyroid hormone 1 receptor (PTHR)
Sorting nexin 27 (SNX27)
Osteoblasts
Bone growth
Bone development
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
Institute for Molecular Bioscience - Publications
 
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