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

Publication Type:

Journal Article


Neuron (2021)


<p>CIB2 is a Ca- and Mg-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 K4 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 K4. Functional studies in mice show that CIB2 regulates TMC1/2 localization and function in hair cells, processes that are affected by deafness-causing CIB2 mutations. We conclude that CIB2 and CIB3 are MET channel auxiliary subunits with striking similarity to K4 channel auxiliary subunits.</p>

Homo sapiens CIB3, Homo sapiens CIB3 EK150QH, and the complex of Homo sapiens CIB3 with Mus musculus TMC1 peptide reported in this paper are PDB: 6WU5, PDB: 6WU7, and PDB: 6WUD, respectively.