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TRPV4 expresses in bone cell lineages and TRPV4-R616Q mutant causing Brachyolmia in human reveals 'loss-of-interaction' with cholesterol
- Source :
- Biochemical and biophysical research communications. 517(4)
- Publication Year :
- 2019
-
Abstract
- Transient receptor potential Vanilloid ion channel sub type 4 (TRPV4) is involved in complex Ca2+-signaling. At least one copy of TRPV4 is present in all vertebrates and is involved in several physiological processes including sensory process and point mutations in TRPV4 leads to development of different pathophysiological disorders in human. R616Q mutant of TRPV4 has been referred as “gain-of-function” mutant causing abnormality in bone cells and develop pathophysiological condition known as “Brachyolmia”. In this work, we demonstrated that R616Q mutation is located in a very critical position of TRPV4 containing a cholesterol-binding motif sequence which is highly conserved in all vertebrates. Accordingly, TRPV4-Wt but not the TRPV4-R616Q localizes preferably in cholesterol-enriched lipid rafts in osteogenic cell line Saos2 and in DRG-neuron derived F11 cell line. Further, FRAP experiment suggest TRPV4-Wt but not the TRPV4-R616Q mutant is more mobile especially in cholesterol-reduced lipid membrane. GST-tagged TM4-Loop-TM5 fragment containing TRPV4-Wt but not R616Q sequence interacts with cholesterol, forms high-molecular weight complex and also show band shift in SDS-PAGE. TRPV4 is expressed in Mesenchymal stem cells and the localization of TRPV4 in lipid raft is dependent on temperature and cholesterol. Our data suggests that TRPV4-R616Q mutant behaves as a “loss-of-interaction” with cholesterol.
- Subjects :
- 0301 basic medicine
TRPV4
Xenopus
Mutant
Amino Acid Motifs
Biophysics
TRPV Cation Channels
Osteochondrodysplasias
Biochemistry
Bone and Bones
03 medical and health sciences
Transient receptor potential channel
0302 clinical medicine
Membrane Microdomains
Cell Movement
Cell Line, Tumor
Bone cell
Animals
Humans
Cell Lineage
Amino Acid Sequence
Lipid bilayer
Molecular Biology
Lipid raft
Ion channel
Conserved Sequence
Neurons
Chemistry
Point mutation
Temperature
Mesenchymal Stem Cells
Cell Biology
Cell biology
030104 developmental biology
Cholesterol
Structural Homology, Protein
030220 oncology & carcinogenesis
Mutation
lipids (amino acids, peptides, and proteins)
Mutant Proteins
Subjects
Details
- ISSN :
- 10902104
- Volume :
- 517
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- Biochemical and biophysical research communications
- Accession number :
- edsair.doi.dedup.....45f73ecad1bf6abc435d24d619b302ac