Sec13, a β-propeller protein, is a core component of multiple complexes, including the COPII endoplasmic reticulum export vesicle coat, the nuclear pore complex (NPC), and the Seh1-associated (SEA)/GATOR nutrient-sensing complex [2]. It plays crucial roles in protein trafficking from the endoplasmic reticulum to the Golgi complex, chromatin organization, transcription, translation, and degradation [4]. These functions are essential for normal cellular activities and have implications for various biological processes and disease-related pathways. Genetic models, such as gene-knockout (KO) and conditional-knockout (CKO) mouse models, are valuable tools for studying Sec13 functions.

In KO/CKO mouse models and other functional studies, ablation of Sec13 in the oligodendrocyte (OL) lineage prevented OPC differentiation, inhibited myelination and remyelination after demyelinating injury in the central nervous system (CNS), as Sec13-dependent protein transport was found essential for OL differentiation and myelin repair. Sec13 loss also altered OL secretome and inhibited pleiotrophin (PTN) secretion, with PTN acting as an autocrine factor for OL differentiation [1]. In an acute lung injury (ALI) mouse model, Sec13 expression increased, promoting glycolysis, epithelial-mesenchymal transition (EMT), and inflammation. Knockdown of Sec13 alleviated ALI by inhibiting Ubqln1-mediated Pgm1 ubiquitination, stabilizing Pgm1 which regulates glucose-6-phosphate (G6P) production [3].

In conclusion, Sec13 is essential for OL differentiation and myelin repair in the CNS, and it also plays a key role in ALI by affecting glycolysis and EMT. The study of Sec13 using KO/CKO mouse models has provided insights into its functions in these specific disease-related processes, highlighting its potential as a therapeutic target for neurological and lung-related diseases.

References:

1. Liu, Zhixiong, Yan, Minbiao, Lei, Wanying, Wang, Zhanxiang, Zhang, Liang. . Sec13 promotes oligodendrocyte differentiation and myelin repair through autocrine pleiotrophin signaling. In The Journal of clinical investigation, 132, . doi:10.1172/JCI155096. https://pubmed.ncbi.nlm.nih.gov/35143418/

2. Faktorová, Drahomíra, Záhonová, Kristína, Benz, Corinna, Field, Mark C, Lukeš, Julius. 2023. Functional differentiation of Sec13 paralogues in the euglenozoan protists. In Open biology, 13, 220364. doi:10.1098/rsob.220364. https://pubmed.ncbi.nlm.nih.gov/37311539/

3. Wu, Dongdong, Zhang, Hui, Li, Fang, Wang, Jiannan, Wu, Qiuge. 2024. Sec13 promotes glycolysis by inhibiting Ubqln1 mediated Pgm1 ubiquitination in ALI. In Biochimica et biophysica acta. Molecular basis of disease, 1870, 167475. doi:10.1016/j.bbadis.2024.167475. https://pubmed.ncbi.nlm.nih.gov/39159700/

4. Anglès, Frédéric, Gupta, Vijay, Wang, Chao, Balch, William E. 2024. COPII cage assembly factor Sec13 integrates information flow regulating endomembrane function in response to human variation. In Scientific reports, 14, 10160. doi:10.1038/s41598-024-60687-2. https://pubmed.ncbi.nlm.nih.gov/38698045/