Evolutionary Analyses Reveal Independent Origins of Gene Repertoires and Structural Motifs Associated to Fast Inactivation in Calcium-selective TRPV Channels
Authors
Affiliations
Essential for calcium homeostasis, TRPV5 and TRPV6 are calcium-selective channels belonging to the transient receptor potential (TRP) gene family. In this study, we investigated the evolutionary history of these channels to add an evolutionary context to the already available physiological information. Phylogenetic analyses revealed that paralogs found in mammals, sauropsids, amphibians, and chondrichthyes, are the product of independent duplication events in the ancestor of each group. Within amniotes, we identified a traceable signature of three amino acids located at the amino-terminal intracellular region. The signature correlates with both the duplication events and the phenotype of fast inactivation observed in mammalian TRPV6 channels. Electrophysiological recordings and mutagenesis revealed that the signature sequence modulates the phenotype of fast inactivation in all clades of vertebrates but reptiles. A transcriptome analysis showed a change in tissue expression from gills, in marine vertebrates, to kidneys in terrestrial vertebrates. Our results highlight a cytoplasmatic structural triad composed by the Helix-Loop-Helix domain, the S2-S3 linker, and the TRP domain helix that is important on modulating the activity of calcium-selective TRPV channels.
The Molecular Biology of Placental Transport of Calcium to the Human Foetus.
Walker V Int J Mol Sci. 2025; 26(1.
PMID: 39796238 PMC: 11720126. DOI: 10.3390/ijms26010383.
Wound Repair and Ca Signalling Interplay: The Role of Ca Channels in Skin.
Bonsignore G, Martinotti S, Ranzato E Cells. 2024; 13(6.
PMID: 38534335 PMC: 10969298. DOI: 10.3390/cells13060491.
Wang Y, Yue Y, Li C, Chen Z, Cai Y, Hu C iScience. 2024; 27(1):108445.
PMID: 38205241 PMC: 10776941. DOI: 10.1016/j.isci.2023.108445.
A cooperative knock-on mechanism underpins Ca2+-selective cation permeation in TRPV channels.
Ives C, Thomson N, Zachariae U J Gen Physiol. 2023; 155(5).
PMID: 36943243 PMC: 10038842. DOI: 10.1085/jgp.202213226.
Flores-Aldama L, Bustos D, Cabezas-Bratesco D, Gonzalez W, Brauchi S Int J Mol Sci. 2023; 24(5).
PMID: 36901904 PMC: 10003196. DOI: 10.3390/ijms24054470.