P2X2 Dominant Deafness Mutations Have No Negative Effect on Wild-Type Isoform: Implications for Functional Rescue and in Deafness Mechanism.

ABSTRACT: The P2X2 receptor is an ATP-gated ion channel, assembled by three subunits. Recently, it has been found that heterozygous mutations of P2X2 V60L and G353R can cause autosomal dominant nonsyndromic hearing loss. However, the underlying mechanism remains unclear. The fact that heterozygous mutations cause deafness suggests that the mutations may have dominant-negative effect (DNE) on wild-type (WT) P2X2 isoforms and/or other partners leading to hearing loss. In this study, the effect of these dominant deafness P2X2 mutations on WT P2X2 was investigated. We found that sole transfection of both V60L and G353R deafness mutants could efficiently target to the plasma membrane, like WT P2X2, but exhibit a significantly reduced response to ATP stimulation. Both mutants reduced the channel conductan

SUBMITTER: Zhu Y 

PROVIDER: S-EPMC5693881 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature