Cap1-KO Mouse

Cap1, also known as Cyclase-Associated Protein 1, is a highly conserved protein with multiple essential functions. It is involved in regulating actin dynamics, which is crucial for various cellular processes such as cell migration, proliferation, and adhesion. Cap1 also participates in cAMP-related signaling pathways, for example, it binds and activates adenylyl cyclase in mammalian cells, modulating cAMP levels and cAMP-dependent proliferation [3]. Additionally, it has been associated with the regulation of innate immune responses through its role in RNA methylation [1]. Genetic models, like gene knockout mouse models, are valuable for studying Cap1's functions.

In lung cancer, knockdown of Cap1 in A549 cells inhibited proliferation and migration, and phosphorylation of specific sites (S308 and S310) in Cap1 promoted lung cancer cell proliferation, migration, and metastasis both in vitro and in vivo [2]. In erythroid differentiation, enforced up-regulation of Cap1 inhibited the formation of contractile actin rings in erythroblasts, preventing their terminal differentiation and enucleation [4]. In colon cancer cells, knockdown of Cap1 led to opposite adhesion phenotypes in different cell lines, and depletion of Cap1 abolished the stimulatory effects of cAMP activators on matrix adhesion, indicating its role in cAMP-Rap1 signaling for adhesion [5]. In the mouse cerebral cortex, inactivation of Cap1 reduced actin monomers in the cytoplasm, promoting nuclear MRTF translocation and MRTF-SRF activation [6].

In conclusion, Cap1 is a key regulator in multiple biological processes. Through model-based research, especially gene knockout mouse models, its role in diseases like cancer, and in biological processes such as erythroid differentiation and cAMP-mediated signaling, has been revealed. These findings contribute to understanding the underlying mechanisms of diseases and may provide potential therapeutic targets.

References:

1. Tsukamoto, Yuta, Igarashi, Manabu, Kato, Hiroki. 2023. Targeting cap1 RNA methyltransferases as an antiviral strategy. In Cell chemical biology, 31, 86-99. doi:10.1016/j.chembiol.2023.11.011. https://pubmed.ncbi.nlm.nih.gov/38091983/

2. Zeng, Jie, Li, Xuan, Liang, Long, Xie, Shuanshuan, Wang, Changhui. 2021. Phosphorylation of CAP1 regulates lung cancer proliferation, migration, and invasion. In Journal of cancer research and clinical oncology, 148, 137-153. doi:10.1007/s00432-021-03819-9. https://pubmed.ncbi.nlm.nih.gov/34636991/

3. Zhang, Xuefeng, Pizzoni, Alejandro, Hong, Kyoungja, Korkhov, Volodymyr, Altschuler, Daniel L. . CAP1 binds and activates adenylyl cyclase in mammalian cells. In Proceedings of the National Academy of Sciences of the United States of America, 118, . doi:10.1073/pnas.2024576118. https://pubmed.ncbi.nlm.nih.gov/34099549/

4. Huang, Xiaoli, Chao, Ruihua, Zhang, Yanyang, Liang, Dongli, Wang, Yuan. 2021. CAP1, a target of miR-144/451, negatively regulates erythroid differentiation and enucleation. In Journal of cellular and molecular medicine, 25, 2377-2389. doi:10.1111/jcmm.16067. https://pubmed.ncbi.nlm.nih.gov/33496386/

5. Ramsey, Auburn, Akana, Lokesh, Miyajima, Erina, Xie, Jennifer Y, Zhou, Guo-Lei. 2023. CAP1 (cyclase-associated protein 1) mediates the cyclic AMP signals that activate Rap1 in stimulating matrix adhesion of colon cancer cells. In Cellular signalling, 104, 110589. doi:10.1016/j.cellsig.2023.110589. https://pubmed.ncbi.nlm.nih.gov/36621727/

6. Khudayberdiev, Sharof, Weiss, Kerstin, Heinze, Anika, Linne, Uwe, Rust, Marco B. 2024. The actin-binding protein CAP1 represses MRTF-SRF-dependent gene expression in mouse cerebral cortex. In Science signaling, 17, eadj0032. doi:10.1126/scisignal.adj0032. https://pubmed.ncbi.nlm.nih.gov/38713765/