Cib3, a member of the calcium-and integrin-binding protein family, is involved in crucial biological functions, especially in the inner ear. It participates in the mechanoelectrical transduction (MET) pathway in hair cells, which is essential for hearing and balance perception. Genetic models, such as mouse models, are valuable for studying its function [1,2,3,4].

In mouse models, Cib3 can functionally substitute for Cib2 in cochlear hair cells. Loss-of-function studies show that Cib2 and Cib3 act redundantly to regulate MET in vestibular hair cells (VHCs). MET currents are completely abolished in VHCs of Cib2/Cib3 double-knock-out mice. Also, Cib2 and Cib3 have different roles in stereocilia maintenance in VHCs. Cib3 transcripts are highly expressed in the extrastriolar region, and its knockout mainly affects stereocilia maintenance in extrastriolar VHCs [1,2].

In conclusion, Cib3 is important for mechanoelectrical transduction and stereocilia maintenance in inner-ear hair cells. Studies using Cib3 knockout mouse models have revealed its role in balance-related functions, providing insights into the molecular mechanisms underlying hearing and balance disorders [1,2,4].

References:

1. Liang, Xiaoping, Qiu, Xufeng, Dionne, Gilman, Shapiro, Lawrence, Müller, Ulrich. 2021. CIB2 and CIB3 are auxiliary subunits of the mechanotransduction channel of hair cells. In Neuron, 109, 2131-2149.e15. doi:10.1016/j.neuron.2021.05.007. https://pubmed.ncbi.nlm.nih.gov/34089643/

2. Wang, Xiaoying, Liu, Shuang, Cheng, Qi, Xiong, Wei, Xu, Zhigang. 2023. CIB2 and CIB3 Regulate Stereocilia Maintenance and Mechanoelectrical Transduction in Mouse Vestibular Hair Cells. In The Journal of neuroscience : the official journal of the Society for Neuroscience, 43, 3219-3231. doi:10.1523/JNEUROSCI.1807-22.2023. https://pubmed.ncbi.nlm.nih.gov/37001993/

3. Giese, Arnaud P J, Weng, Wei-Hsiang, Kindt, Katie S, Sotomayor, Marcos, Ahmed, Zubair M. 2024. Complexes of vertebrate TMC1/2 and CIB2/3 proteins form hair-cell mechanotransduction cation channels. In bioRxiv : the preprint server for biology, , . doi:10.1101/2023.05.26.542533. https://pubmed.ncbi.nlm.nih.gov/37398045/

4. Wang, Xiaoying, Yi, Zhangyi, Shi, Mengwen, Sun, Yu. 2025. The Diverse Functions of the Calcium- and Integrin-Binding Protein Family. In International journal of molecular sciences, 26, . doi:10.3390/ijms26052223. https://pubmed.ncbi.nlm.nih.gov/40076845/