Abstract
| Original language | English |
|---|---|
| Pages (from-to) | 1367-1382 |
| Number of pages | 16 |
| Journal | Molecular Biology of the Cell |
| Volume | 27 |
| Issue number | 8 |
| DOIs | |
| Publication status | Published - 15 Apr 2016 |
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Sorting nexin 27 couples PTHR trafficking to retromer for signal regulation in osteoblasts during bone growth. / Chan, Audrey; Clairfeuille, T.; Landao-Bassonga, Euphemie; Kinna, G.; Ng, Pei Ying; Loo, L.S.; Cheng, Tak Sum; Zheng, Minghao; Hong, W.; Teasdale, R.D.; Collins, B.M.; Pavlos, Nathan.
In: Molecular Biology of the Cell, Vol. 27, No. 8, 15.04.2016, p. 1367-1382.Research output: Contribution to journal › Article
TY - JOUR
T1 - Sorting nexin 27 couples PTHR trafficking to retromer for signal regulation in osteoblasts during bone growth
AU - Chan, Audrey
AU - Clairfeuille, T.
AU - Landao-Bassonga, Euphemie
AU - Kinna, G.
AU - Ng, Pei Ying
AU - Loo, L.S.
AU - Cheng, Tak Sum
AU - Zheng, Minghao
AU - Hong, W.
AU - Teasdale, R.D.
AU - Collins, B.M.
AU - Pavlos, Nathan
PY - 2016/4/15
Y1 - 2016/4/15
N2 - © 2016 Billmann, Horn, et al. 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.
AB - © 2016 Billmann, Horn, et al. 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.
U2 - 10.1091/mbc.E15-12-0851
DO - 10.1091/mbc.E15-12-0851
M3 - Article
VL - 27
SP - 1367
EP - 1382
JO - Molecular Biology of the Cell
JF - Molecular Biology of the Cell
SN - 1044-2030
IS - 8
ER -