| First Author | Liang X | Year | 2021 |
| Journal | Neuron | Volume | 109 |
| Issue | 13 | Pages | 2131-2149.e15 |
| PubMed ID | 34089643 | Mgi Jnum | J:307668 |
| Mgi Id | MGI:6720576 | Doi | 10.1016/j.neuron.2021.05.007 |
| Citation | Liang X, et al. (2021) CIB2 and CIB3 are auxiliary subunits of the mechanotransduction channel of hair cells. Neuron 109(13):2131-2149.e15 |
| abstractText | CIB2 is a Ca(2+)- and Mg(2+)-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 Kv4 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 Kv4. 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 Kv4 channel auxiliary subunits. |
