CIB2 and CIB3 are auxiliary subunits of the mechanotransduction channel of hair cells.

ABSTRACT: CIB2 is a Ca²⁺- and Mg²⁺-binding protein essential for mechanoelectrical transduction (MET) by cochlear hair cells, but not by vestibular hair cells that co-express CIB2 and CIB3. Here, we show that in cochlear hair cells, CIB3 can functionally substitute for CIB2. Using X-ray crystallography, we demonstrate that CIB2 and CIB3 are structurally similar to KChIP proteins, auxiliary subunits of voltage-gated K_v4 channels. CIB2 and CIB3 bind to TMC1/2 through a domain in TMC1/2 flanked by transmembrane domains 2 and 3. The co-crystal structure of the CIB-binding domain in TMC1 with CIB3 reveals that interactions are mediated through a conserved CIB hydrophobic groove, similar to KChIP1 binding of K_v4. Functional studies in mice show that CIB2 regulat

SUBMITTER: Liang X 

PROVIDER: S-EPMC8374959 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature