Evolution of the voltage sensor domain of the voltage-sensitive phosphoinositide phosphatase, VSP/TPTE, suggests a role as a proton channel in eutherian mammals
- Authors
- Sutton, K.A., Jungnickel, M.K., Jovine, L., and Florman, H.M.
- ID
- ZDB-PUB-120314-6
- Date
- 2012
- Source
- Mol. Biol. Evol. 29(9): 2147-2155 (Journal)
- Registered Authors
- Keywords
- voltage sensor domain, proton channel, ion channel, phosphoinositide phosphatase, sperm
- MeSH Terms
-
- Amino Acid Sequence
- Animals
- Cell Line
- Evolution, Molecular*
- Humans
- Membrane Potentials/physiology
- Membrane Proteins/chemistry
- Membrane Proteins/physiology*
- Models, Molecular
- Molecular Sequence Data
- PTEN Phosphohydrolase/chemistry
- PTEN Phosphohydrolase/physiology*
- Patch-Clamp Techniques
- Protein Interaction Domains and Motifs
- Protein Structure, Tertiary
- Proton Pumps/physiology
- Sequence Alignment
- PubMed
- 22396523 Full text @ Mol. Biol. Evol.
The voltage-sensitive phosphoinositide phosphatases provide a mechanism to couple changes in the transmembrane electrical potential to intracellular signal transduction pathways. These proteins share a domain architecture that is conserved in deuterostomes. However, gene duplication events in primates, including human, give rise to the paralogs TPTE and TPTE2 that retain protein domain organization but, in the case of TPTE, have lost catalytic activity. Here, we present evidence that these human proteins contain a functional voltage sensor, similar to that in non-mammalian orthologs. However, domains of these human proteins can also generate a non-inactivating outward current that is not observed in zebrafish or tunicate orthologs. This outward current has the anticipated characteristics of a voltage-sensitive proton current and is due to the appearance of a single histidine residue in the S4 transmembrane segment of the voltage sensor. Histidine is observed at this position only during the eutherian radiation. Domains from both human paralogs generate proton currents. This apparent gain of proton channel function during the evolution of the TPTE protein family may account for the conservation of voltage sensor domains despite the loss of phosphatase activity in some human paralogs.