Dephosphorylation of the NPR2 guanylyl cyclase contributes to inhibition of bone growth by fibroblast growth factor

Activating mutations in fibroblast growth factor (FGF) receptor 3 and inactivating mutations in the NPR2 guanylyl cyclase both cause severe short stature, but how these two signaling systems interact to regulate bone growth is poorly understood. Here, we show that bone elongation is increased when N...

Full description

Saved in:
Bibliographic Details
Published in:eLife 2017-12, Vol.6
Main Authors: Shuhaibar, Leia C, Robinson, Jerid W, Vigone, Giulia, Shuhaibar, Ninna P, Egbert, Jeremy R, Baena, Valentina, Uliasz, Tracy F, Kaback, Deborah, Yee, Siu-Pok, Feil, Robert, Fisher, Melanie C, Dealy, Caroline N, Potter, Lincoln R, Jaffe, Laurinda A
Format: Article
Language:English
Subjects:
Achondroplasia
Age
Bone growth
Bones
chondrocyte
Chondrocytes
Cyclic GMP
Cyclic guanosine monophosphate
Dephosphorylation
Developmental Biology
Dwarfism
Elongation
Enzymes
fibroblast growth factor
Fibroblast growth factors
Genetically modified organisms
Growth factors
Growth plate
Guanylate cyclase
House mouse
Image processing equipment
Imaging systems
Microscopy
Mutation
NPR2 guanylyl cyclase
Peptides
Phosphatases
Phosphates
Phosphorylation
Proteins
Sensors
Short stature
Tibia
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Activating mutations in fibroblast growth factor (FGF) receptor 3 and inactivating mutations in the NPR2 guanylyl cyclase both cause severe short stature, but how these two signaling systems interact to regulate bone growth is poorly understood. Here, we show that bone elongation is increased when NPR2 cannot be dephosphorylated and thus produces more cyclic GMP. By developing an in vivo imaging system to measure cyclic GMP production in intact tibia, we show that FGF-induced dephosphorylation of NPR2 decreases its guanylyl cyclase activity in growth plate chondrocytes in living bone. The dephosphorylation requires a PPP-family phosphatase. Thus FGF signaling lowers cyclic GMP production in the growth plate, which counteracts bone elongation. These results define a new component of the signaling network by which activating mutations in the FGF receptor inhibit bone growth.
ISSN:2050-084X
2050-084X
DOI:10.7554/elife.31343