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

被引：42

作者：

Chan, Audrey S. M. ^{[1
]}

Clairfeuille, Thomas ^{[2
]}

Landao-Bassonga, Euphemie ^{[1
]}

Kinna, Genevieve ^{[2
]}

Ng, Pei Ying ^{[1
]}

Loo, Li Shen ^{[3
]}

Cheng, Tak Sum ^{[1
]}

Zheng, Minghao ^{[1
]}

Hong, Wanjin ^{[3
]}

Teasdale, Rohan D. ^{[2
]}

Collins, Brett M. ^{[2
]}

Pavlos, Nathan J. ^{[1
]}

机构：

[1] Univ Western Australia, Sch Surg, Cellular Orthopaed Lab, Nedlands, WA 6009, Australia

[2] Univ Queensland, Inst Mol Biosci, St Lucia, Qld 4072, Australia

[3] ASTAR, Inst Mol & Cell Biol, Singapore 138673, Singapore

来源：

MOLECULAR BIOLOGY OF THE CELL | 2016年 / 27卷 / 08期

基金：

英国医学研究理事会; 澳大利亚研究理事会;

关键词：

PARATHYROID-HORMONE RECEPTOR; PDZ DOMAIN INTERACTION; METAPHYSEAL CHONDRODYSPLASIA; TARGETED DISRUPTION; POTASSIUM CHANNELS; PARKINSON DISEASE; PROTEIN-RECEPTOR; TRABECULAR BONE; BETA-ARRESTIN; COMPLEX;

D O I：

10.1091/mbc.E15-12-0851

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：1367 / 1382

页数：16

共 1 条

[1] A role for sorting nexin 2 in epidermal growth factor receptor down-regulation: Evidence for distinct functions of sorting nexin 1 and 2 in protein trafficking
Gullapalli, A
Garrett, TA
Paing, MM
Griffin, CT
Yang, YH
Trejo, J
MOLECULAR BIOLOGY OF THE CELL, 2004, 15 (05) : 2143 - 2155

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