Scgn, or secretagogin, is a calcium sensor protein. It is expressed in neuroendocrine lineages and is involved in regulating synaptic transmission, interacting with the SNARE complex for vesicle fusion [2,5]. It also plays roles in calcium-dependent interactions regulating insulin secretion, and has been implicated in various biological pathways related to neuroendocrine functions [7]. Genetic models such as gene knockout in zebrafish or mice are valuable for studying its functions.

Deletion of Scgn in zebrafish or mice leads to autism-like behaviors, impairs brain development, disrupts oxytocin signaling, and abnormally activates inflammation, suggesting its role in autism spectrum disorder (ASD) [1]. In mice, Scgn deficiency results in impaired hormone release and susceptibility to DSS-induced colitis, indicating its link to colitis susceptibility [2]. In clear cell renal cell carcinoma (ccRCC), studies on cell lines overexpressing Scgn show it can regulate cytokine/chemokine secretion, recruit M1-type macrophages, and is associated with prognosis, with high Scgn expression potentially indicating a better prognosis [3,4,8]. In type 2 diabetes, lipotoxicity-induced down-regulation of Scgn in islet β-cells promotes NLRP3-mediated β-cell pyroptosis, and restoring Scgn can reverse this [6].

In conclusion, Scgn is crucial in multiple biological processes. Gene knockout models in zebrafish and mice have revealed its significance in ASD, colitis, and β-cell function in diabetes. In ccRCC, functional studies on cell lines provide insights into its role in tumor microenvironment regulation and prognosis. These findings enhance our understanding of Scgn's biological functions and its implications in various diseases.

References:

1. Liu, Zhe, Tan, Shuai, Zhou, Lianyu, Mo, Xianming, Jia, Da. 2023. SCGN deficiency is a risk factor for autism spectrum disorder. In Signal transduction and targeted therapy, 8, 3. doi:10.1038/s41392-022-01225-2. https://pubmed.ncbi.nlm.nih.gov/36588101/

2. Sifuentes-Dominguez, Luis F, Li, Haiying, Llano, Ernesto, Jia, Da, Burstein, Ezra. 2019. SCGN deficiency results in colitis susceptibility. In eLife, 8, . doi:10.7554/eLife.49910. https://pubmed.ncbi.nlm.nih.gov/31663849/

3. Lai, Chong, Gong, Jingwen, Tang, Jinlong, Zhang, Dandan, Teng, Xiaodong. 2023. SCGN and STAT3 expressions are associated with the prognosis of ccRCC. In Pathology, research and practice, 252, 154940. doi:10.1016/j.prp.2023.154940. https://pubmed.ncbi.nlm.nih.gov/37977033/

4. Guo, Tuanjie, Zhang, Xinchao, Wang, Xuan, Wang, Xu, Wang, Xiang. 2024. SCGN recruits macrophages by regulating chemokine secretion in clear cell renal cell carcinoma. In International journal of biological sciences, 20, 5925-5938. doi:10.7150/ijbs.103252. https://pubmed.ncbi.nlm.nih.gov/39664565/

5. Lv, Ying, Xiang, Sunmin, Cao, Renxian, Wu, Li, Yang, Jing. 2020. SCGN-regulated Stage-wise SNARE Assembly: Novel Insight into Synaptic Exocytosis. In Neuroscience bulletin, 36, 1576-1578. doi:10.1007/s12264-020-00590-8. https://pubmed.ncbi.nlm.nih.gov/33025412/

6. Ouyang, Shuhui, Xiang, Sunmin, Wang, Xin, Fan, Gang, Yang, Jing. 2024. The downregulation of SCGN induced by lipotoxicity promotes NLRP3-mediated β-cell pyroptosis. In Cell death discovery, 10, 340. doi:10.1038/s41420-024-02107-y. https://pubmed.ncbi.nlm.nih.gov/39068218/

7. Sharma, Anand Kumar, Khandelwal, Radhika, Sharma, Yogendra. 2019. Veiled Potential of Secretagogin in Diabetes: Correlation or Coincidence? In Trends in endocrinology and metabolism: TEM, 30, 234-243. doi:10.1016/j.tem.2019.01.007. https://pubmed.ncbi.nlm.nih.gov/30772140/

8. Guo, Tuanjie, Wang, Xuan, Wang, Tao, Wang, Chaofu, Wang, Xiang. 2024. Dynamic changes of SCGN expression imply different phases of clear cell renal cell carcinoma progression. In Discover oncology, 15, 205. doi:10.1007/s12672-024-01071-4. https://pubmed.ncbi.nlm.nih.gov/38831128/