Document Type
Article
Publication Date
7-8-2020
Keywords
JMG
JAX Source
PLoS Genet 2020 Jul 8; 16(7):e1008884
Volume
16
Issue
7
First Page
1008884
Last Page
1008884
ISSN
1553-7404
PMID
32639996
DOI
https://doi.org/10.1371/journal.pgen.1008884
Abstract
The membrane protein ANKH was known to prevent pathological mineralization of joints and was thought to export pyrophosphate (PPi) from cells. This did not explain, however, the presence of ANKH in tissues, such as brain, blood vessels and muscle. We now report that in cultured cells ANKH exports ATP, rather than PPi, and, unexpectedly, also citrate as a prominent metabolite. The extracellular ATP is rapidly converted into PPi, explaining the role of ANKH in preventing ankylosis. Mice lacking functional Ank (Ankank/ank mice) had plasma citrate concentrations that were 65% lower than those detected in wild type control animals. Consequently, citrate excretion via the urine was substantially reduced in Ankank/ank mice. Citrate was even undetectable in the urine of a human patient lacking functional ANKH. The hydroxyapatite of Ankank/ank mice contained dramatically reduced levels of both, citrate and PPi and displayed diminished strength. Our results show that ANKH is a critical contributor to extracellular citrate and PPi homeostasis and profoundly affects bone matrix composition and, consequently, bone quality.
Recommended Citation
Szeri F,
Lundkvist S,
Donnelly S,
Engelke U,
Rhee K,
Williams C,
Sundberg J,
Wevers R,
Tomlinson R,
Jansen R,
van de Wetering K.
The membrane protein ANKH is crucial for bone mechanical performance by mediating cellular export of citrate and ATP. PLoS Genet 2020 Jul 8; 16(7):e1008884
Comments
This is an open access article distributed under the terms of the Creative Commons Attribution License.