CIB2 and CIB3 Regulate Stereocilia Maintenance and Mechanoelectrical Transduction in Mouse Vestibular Hair Cells

Abstract

The mechanoelectrical transduction (MET) protein complex in the inner-ear hair cells is essential for hearing and balance perception. Calcium and integrin-binding protein 2 (CIB2) has been reported to be a component of MET complex, and loss of CIB2 completely abolishes MET currents in auditory hair cells, causing profound congenital hearing loss. However, loss of CIB2 does not affect MET currents in vestibular hair cells (VHCs) as well as general balance function. Here, we show that CIB2 and CIB3 act redundantly to regulate MET in VHCs, as MET currents are completely abolished in the VHCs ofCib2/Cib3double knock-out mice of either sex. Furthermore, we show thatCib2andCib3transcripts have complementary expression patterns in the vestibular maculae, and that they play different roles in stereocilia maintenance in VHCs.Cib2transcripts are highly expressed in the striolar region, and knock-out ofCib2affects stereocilia maintenance in striolar VHCs. In contrast,Cib3transcripts are highly expressed in the extrastriolar region, and knock-out ofCib3mainly affects stereocilia maintenance in extrastriolar VHCs. Simultaneous knock-out ofCib2andCib3affects stereocilia maintenance in all VHCs and leads to severe balance deficits. Taken together, our present work reveals that CIB2 and CIB3 are important for stereocilia maintenance as well as MET in mouse VHCs.SIGNIFICANCE STATEMENTCalcium and integrin-binding protein 2 (CIB2) is an important component of mechanoelectrical transduction (MET) complex, and loss of CIB2 completely abolishes MET in auditory hair cells. However, MET is unaffected inCib2knock-out vestibular hair cells (VHCs). In the present work, we show that CIB3 could compensate for the loss of CIB2 in VHCs, andCib2/Cib3double knock-out completely abolishes MET in VHCs. Interestingly, CIB2 and CIB3 could also regulate VHC stereocilia maintenance in a nonredundant way.Cib2andCib3transcripts are highly expressed in the striolar and extrastriolar regions, respectively. Stereocilia maintenance and balance function are differently affected inCib2orCib3knock-out mice. In conclusion, our data suggest that CIB2 and CIB3 are important for stereocilia maintenance and MET in mouse VHCs.