In:
eLife, eLife Sciences Publications, Ltd, Vol. 6 ( 2017-12-04)
Abstract:
Between birth and puberty, the bones of mammals grow drastically in length. This process is controlled by many proteins, and mutations affecting these proteins can cause bones to either be too long or too short. For example, mutations of a protein called the fibroblast growth factor receptor, or FGF for short, and a protein called NPR2, can cause similar forms of dwarfism – a condition characterized by short stature. The FGF protein controls bone growth, and people with overactive receptors for FGF suffer from a form of dwarfism known as achondroplasia, while people that lack FGF receptors have longer bones. The NPR2 protein, on the other hand, produces a molecule called cGMP, which is necessary for the bones to grow. When NPR2 is blocked, less cGMP is produced, which results in shorter limbs. Previous studies of bone cells grown in the laboratory have shown that these two proteins are linked by a chain of chemical messages. When the FGF receptor is active, phosphate molecules are removed from the NPR2 protein, which reduces the amount of GMP produced. However, until now it was not known whether this mechanism also controls growth in actual bones. Here, Shuhaibar et al. used genetically modified mice in which the phosphate group could not be removed from their NPR2 enzyme. As a result, the bones of these mice were longer than usual. Shuhaibar et al. then developed an imaging technique to examine the region in the bone were growth happens. To see whether FGF reduces the amount of cGMP produced by NPR2 in these areas, cGMP was detected with a fluorescent sensor in order to be tracked. In normal mice, the FGF receptor reduced the rate at which cGMP was produced, but in mice with mutated NPR2, this did not happen. When the cells could not remove the phosphates from NPR2, cGMP levels stayed high and the bones grew longer. These findings reveal new insights into the molecular causes of dwarfism. The next step will be to identify the enzyme responsible for removing phosphate from NPR2. Blocking its activity could help to enhance bone growth. In the future, this could lead to new drug treatments for achondroplasia.
Type of Medium:
Online Resource
ISSN:
2050-084X
DOI:
10.7554/eLife.31343.001
DOI:
10.7554/eLife.31343.002
DOI:
10.7554/eLife.31343.003
DOI:
10.7554/eLife.31343.004
DOI:
10.7554/eLife.31343.005
DOI:
10.7554/eLife.31343.006
DOI:
10.7554/eLife.31343.007
DOI:
10.7554/eLife.31343.008
DOI:
10.7554/eLife.31343.011
DOI:
10.7554/eLife.31343.009
DOI:
10.7554/eLife.31343.010
DOI:
10.7554/eLife.31343.012
DOI:
10.7554/eLife.31343.013
DOI:
10.7554/eLife.31343.014
DOI:
10.7554/eLife.31343.015
DOI:
10.7554/eLife.31343.016
DOI:
10.7554/eLife.31343.017
DOI:
10.7554/eLife.31343.019
DOI:
10.7554/eLife.31343.020
Language:
English
Publisher:
eLife Sciences Publications, Ltd
Publication Date:
2017
detail.hit.zdb_id:
2687154-3
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