Shisa8, also known as CKAMP39, is a member of the Cystine-knot AMPA receptor-modulating proteins (CKAMPs) family. It influences the trafficking, subcellular localization and function of AMPA receptors, which are assembled of four core subunits and several interacting proteins. These functions play a significant role in neural-related biological processes [1].

A multi-omics analysis of expeditioners in Antarctica identified Shisa Family Member 8 (SHISA8) as a potential key regulatory hub in modulating human sleep-wake activity. During the austral winter, expeditioners had sleep disruptions, and through correlation and causal mediation analysis, SHISA8 was revealed as a candidate gene related to these sleep-wake changes, suggesting it may be a novel target for medical intervention in sleep disorders under unique light environments [2].

In the study of lateral branch nephrogenesis, new, age-specific rhesus nephron progenitor cells (SHISA8) were discovered. The rhesus macaque was used as a model, and the findings in rhesus were verified in late-gestation human archival samples, indicating SHISA8 may be involved in nephrogenesis-related molecular processes [3].

In conclusion, Shisa8 is crucial for the regulation of AMPA receptor function, potentially plays a role in sleep-wake activity regulation under unique light conditions, and may be involved in nephrogenesis. Research on Shisa8 using models like the rhesus macaque and through multi-omics analysis provides insights into its functions in neural-related, sleep-related, and kidney-related biological processes, which could potentially contribute to understanding and treating related disorders.

References:

1. von Engelhardt, Jakob. 2019. AMPA Receptor Auxiliary Proteins of the CKAMP Family. In International journal of molecular sciences, 20, . doi:10.3390/ijms20061460. https://pubmed.ncbi.nlm.nih.gov/30909450/

2. Liu, Shiying, Wang, Jianan, Tian, Xuan, Wu, Xiaopei, Xu, Chengli. 2024. An integrated multi-omics analysis identifies novel regulators of circadian rhythm and sleep disruptions under unique light environment in Antarctica. In Molecular psychiatry, , . doi:10.1038/s41380-024-02844-7. https://pubmed.ncbi.nlm.nih.gov/39587296/

3. Schuh, Meredith P, Alkhudairy, Lyan, Potter, Andrew, Salomonis, Nathan, Kopan, Raphael. 2021. The Rhesus Macaque Serves As a Model for Human Lateral Branch Nephrogenesis. In Journal of the American Society of Nephrology : JASN, 32, 1097-1112. doi:10.1681/ASN.2020101459. https://pubmed.ncbi.nlm.nih.gov/33789950/