Cc2d1b, a member of the Lgd/CC2D1 family of proteins, is highly expressed in myelinating cells in the central and peripheral nervous systems. It is involved in multiple biological processes, including myelination, nuclear envelope reformation, and may play a role in the regulation of transmembrane receptor degradation and signaling [1,2,4]. Its study via genetic models is crucial to understand these functions.

In a Cc2d1b constitutive knockout mouse model, while no myelin thickness difference was observed in the peripheral nervous system, optic nerves in the central nervous system showed hypomyelination of large diameter myelinated fibers, suggesting its role in developmental myelination in the central nervous system [1]. Also, silencing Cc2d1b in Schwann cells limits the formation of myelin segments, indicating its importance in myelin gene transcriptional network [3]. In cell models, depletion of Cc2d1b accelerates the degradation of EGFR and TLR4 and their downstream signaling, suggesting its role in preventing premature sorting of these receptors to lysosomes [4]. Additionally, in human studies, a rare and deleterious variant of Cc2d1b was found in infertile men with abnormal sperm head, suggesting its potential role in sperm head formation [5].

In conclusion, Cc2d1b plays essential roles in developmental myelination in the central nervous system, myelin gene transcription in Schwann cells, regulation of transmembrane receptor degradation and signaling, and potentially in sperm head formation. The use of Cc2d1b knockout mouse models and human genetic studies has significantly contributed to understanding its functions in these biological processes and disease-related conditions such as male infertility.

References:

1. Acheta, Jenica, Hong, Jiayue, Jeanette, Haley, Belin, Sophie, Poitelon, Yannick. 2022. Cc2d1b Contributes to the Regulation of Developmental Myelination in the Central Nervous System. In Frontiers in molecular neuroscience, 15, 881571. doi:10.3389/fnmol.2022.881571. https://pubmed.ncbi.nlm.nih.gov/35592111/

2. Ventimiglia, Leandro N, Cuesta-Geijo, Miguel Angel, Martinelli, Nicolas, Weissenhorn, Winfried, Martin-Serrano, Juan. . CC2D1B Coordinates ESCRT-III Activity during the Mitotic Reformation of the Nuclear Envelope. In Developmental cell, 47, 547-563.e6. doi:10.1016/j.devcel.2018.11.012. https://pubmed.ncbi.nlm.nih.gov/30513301/

3. Sophie, Belin, Jacob, Herron, Jordan, VerPlank J S, Laura, Feltri M, Yannick, Poitelon. 2019. YAP and TAZ Regulate Cc2d1b and Purβ in Schwann Cells. In Frontiers in molecular neuroscience, 12, 177. doi:10.3389/fnmol.2019.00177. https://pubmed.ncbi.nlm.nih.gov/31379499/

4. Deshar, Rakesh, Cho, Eun-Bee, Yoon, Sungjoo Kim, Yoon, Jong-Bok. 2016. CC2D1A and CC2D1B regulate degradation and signaling of EGFR and TLR4. In Biochemical and biophysical research communications, 480, 280-287. doi:10.1016/j.bbrc.2016.10.053. https://pubmed.ncbi.nlm.nih.gov/27769858/

5. Li, Yaqian, Wang, Yan, Wen, Yuting, Yang, Yihong, Shen, Ying. . Whole-exome sequencing of a cohort of infertile men reveals novel causative genes in teratozoospermia that are chiefly related to sperm head defects. In Human reproduction (Oxford, England), 37, 152-177. doi:10.1093/humrep/deab229. https://pubmed.ncbi.nlm.nih.gov/34791246/