Cib2, or calcium and integrin binding family member 2 protein, is a small EF-hand protein capable of binding Mg2+ and Ca2+ ions. It is an essential component of the mechano-transduction machinery in cochlear hair cells and is involved in processes like integrin signaling, autophagy, and maintaining Ca2+ homeostasis in cells [4,5]. It has been associated with multiple biological pathways such as the calcium signaling pathway in the inner ear and pathways related to cell adhesion, migration, and signaling activation via integrins [5].

Genetically modified mouse models, including cardiomyocyte-specific Cib2 knockout (Cib2-/-) and atrial myocyte-specific Cib2-overexpressing models, have been used to study Cib2's function. In the context of atrial fibrillation (AF), loss of Cib2 in mouse models enhances AF occurrence, prolongs AF duration, and increases atrial fibrosis under stress, while Cib2 overexpression mitigates these effects. Cib2 was found to compete with and inhibit CIB1-mediated calcineurin activation, thus protecting against atrial remodeling and AF [1]. In inner-ear research, Cib2 knockout in mice completely abolishes mechanoelectrical transduction (MET) currents in auditory hair cells, causing profound congenital hearing loss. However, in vestibular hair cells, CIB3 can compensate for the loss of CIB2, though Cib2/Cib3 double-knockout mice have abolished MET currents in vestibular hair cells and show severe balance deficits [2,3].

In conclusion, Cib2 is crucial for mechanoelectrical transduction in hair cells, maintaining the normal function of the inner ear, and plays a protective role against atrial remodeling and AF. The use of Cib2 knockout and over-expressing mouse models has significantly advanced our understanding of its functions in hearing-related processes and cardiac diseases like AF.

References:

1. Wang, Yihui, Wang, Jizheng, Shi, Ling, Song, Lei, Zhao, Shihua. 2023. CIB2 Is a Novel Endogenous Repressor of Atrial Remodeling. In Circulation, 147, 1758-1776. doi:10.1161/CIRCULATIONAHA.122.062660. https://pubmed.ncbi.nlm.nih.gov/37128899/

2. 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/

3. 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/

4. Dal Cortivo, Giuditta, Dell'Orco, Daniele. 2022. Calcium- and Integrin-Binding Protein 2 (CIB2) in Physiology and Disease: Bright and Dark Sides. In International journal of molecular sciences, 23, . doi:10.3390/ijms23073552. https://pubmed.ncbi.nlm.nih.gov/35408910/

5. Jacoszek, Agnieszka, Pollak, Agnieszka, Płoski, Rafał, Ołdak, Monika. 2016. Advances in genetic hearing loss: CIB2 gene. In European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery, 274, 1791-1795. doi:10.1007/s00405-016-4330-9. https://pubmed.ncbi.nlm.nih.gov/27771768/