Changes in Cochlear PMCA2 Expression Correlate with the Maturation of Auditory Sensitivity

Abstract

The plasma membrane Ca 2+ ATPase 2 (PMCA2) is necessary for auditory transduction and serves as the primary Ca 2+ extrusion mechanism in auditory stereocilia bundles. To date, studies examining PMCA2 in auditory function using mutant mice have focused on the phenotype of late adolescent and adult mice. Here, we focus on the changes of PMCA2 in the maturation of auditory sensitivity by comparing auditory responses to RNA and protein expression levels in haploinsufficient PMCA2 and wild-type mice from P16 into adulthood. Auditory sensitivity in wild-type mice improves between P16 and 3 weeks of age, when it becomes stable through adolescence. In haploinsufficient mice, there are frequency-dependent loss of sensitivity and subsequent recovery of thresholds between P16 and adulthood. RNA analysis demonstrates that α-Atp2b2 transcript levels increase in both wild-type and heterozygous cochleae between P16 and 5 weeks. The increases reported for the α-Atp2b2 transcript type during this stage in development support the requisite usage of this transcript for mature auditory transduction. PMCA2 expression also increases in wild-type cochleae between P16 and 5 weeks suggesting that this critical auditory protein may be involved in normal maturation of auditory sensitivity after the onset of hearing. We also characterize expression levels of two long noncoding RNA genes, Gm15082 (lnc82) and Gm15083 (lnc83), which are transcribed on the opposite strand in the 5′ region of Atp2b2 and propose that the lnc83 transcript may be involved in regulating α-Atp2b2 expression.

Prestin Contributes to Membrane Compartmentalization and Is Required for Normal Innervation of Outer Hair Cells

“…Thus, in the absence of prestin, apical targeting of PMCA2 is less effective as in immature WT-OHCs, which may be due to stalling along the transcytotic pathway. As the expression of PMCA2 is reported to increase after the onset of hearing ( Watson et al, 2014 ), we examined PMCA2 protein levels in WT ( n = 6) and prestin-KO ( n = 7) cochleae by Western blot. As shown in Figure 2B , there are no significant differences in PMCA2 expression levels in WT and prestin-KO cochleae, suggesting the prestin-KO mice retain mature levels of PMCA2 protein.…”

The Genomics of Auditory Function and Disease

“…A handful of studies have characterized the expression profiles of lncRNAs in the inner ear by using high-throughput sequencing technologies ( 83 , 105 , 147 , 164 , 176 ). Some inner-ear lncRNAs are also expressed in other systems, such as Malat1 , while others, such as Xloc_012867 , are novel lncRNAs that are apparently restricted to the inner ear ( 83 ).…”