Scgn, or secretagogin, is a calcium sensor protein that is crucial for regulating synaptic transmission and is involved in vesicle fusion with the plasma membrane by interacting with the SNARE complex [2,3]. It is enriched in neuroendocrine cells, including pancreatic β -cells, and is involved in pathways related to insulin secretion, oxytocinergic activities, and immune responses, playing an important role in normal physiological functions [1,5]. Genetic models, such as gene knockout mouse models, are valuable for studying its functions.

In gene knockout models, deletion of Scgn in zebrafish or mice leads to autism-like behaviors and impairs brain development. Mechanistically, Scgn deficiency disrupts oxytocin signaling and abnormally activates inflammation, and ASD probands with Scgn mutations also have reduced oxytocin levels [1]. In mouse models of Scgn deficiency, there is impaired hormone release and increased susceptibility to DSS-induced colitis, indicating a role in intestinal inflammation [2]. In islet β -cells, lipotoxicity-induced down-regulation of Scgn promotes NLRP3-mediated β-cell pyroptosis, and restoring Scgn can reverse this effect [4].

In conclusion, Scgn plays essential roles in synaptic function, hormone release, and immune-related processes. Gene knockout mouse models have revealed its significance in diseases such as autism spectrum disorder, colitis, and type 2 diabetes, highlighting its potential as a therapeutic target for these conditions.

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. 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/

4. 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/

5. 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/