Snx1-KO Mouse

Snx1, a member of the sorting nexin (SNX) family, is crucial for membrane remodeling and endosomal transport [1,2,5]. It has a role in generating transport carriers in endosomal pathways, and its functions are associated with the retromer complex and endosomal SNX-BAR sorting complex for promoting exit 1 complex trafficking [1,2]. Genetic models like knockout mice can provide insights into its specific functions.

In Parkinson's disease models, dysregulation of the SNX1-retromer axis was observed. Stagnation of retromer-mediated retrograde transport occurred in different PD-mimetic conditions. DNAJC13 was involved in clathrin-dependent retromer transport as a functional modulator of SNX1, and excess α-synuclein decreased the interaction between SNX1 and VPS35, a core component of retromer. R33, a pharmacological retromer chaperone, reduced insoluble α-synuclein and mitigated rotenone-induced neuronal apoptosis, suggesting SNX1-retromer-regulated retrograde transport may be involved in PD pathogenesis [4]. In gefitinib-resistant NSCLC cell lines, overexpressed Snx1 was associated with impaired EGFR endocytosis, where internalized EGFR aggregated in early endosomes, implicating dysregulated EGFR endocytosis in gefitinib resistance [3].

In conclusion, Snx1 is essential for endosomal membrane remodeling and transport. Through model-based research, its role in diseases like Parkinson's disease and NSCLC drug resistance has been revealed. These findings highlight Snx1 as a potential target for disease-modifying therapies in these disease areas.

References:

1. Zhang, Yan, Pang, Xiaoyun, Li, Jian, Hsu, Victor W, Sun, Fei. . Structural insights into membrane remodeling by SNX1. In Proceedings of the National Academy of Sciences of the United States of America, 118, . doi:10.1073/pnas.2022614118. https://pubmed.ncbi.nlm.nih.gov/33658379/

2. Da Graça, Juliane, Morel, Etienne. 2023. Canonical and Non-Canonical Roles of SNX1 and SNX2 in Endosomal Membrane Dynamics. In Contact (Thousand Oaks (Ventura County, Calif.)), 6, 25152564231217867. doi:10.1177/25152564231217867. https://pubmed.ncbi.nlm.nih.gov/38033809/

3. Nishimura, Yukio, Itoh, Kazuyuki. 2019. Involvement of SNX1 in regulating EGFR endocytosis in a gefitinib-resistant NSCLC cell lines. In Cancer drug resistance (Alhambra, Calif.), 2, 539-549. doi:10.20517/cdr.2019.15. https://pubmed.ncbi.nlm.nih.gov/35582586/

4. Yoshida, Shun, Hasegawa, Takafumi, Nakamura, Takaaki, Takeda, Atsushi, Aoki, Masashi. 2024. Dysregulation of SNX1-retromer axis in pharmacogenetic models of Parkinson's disease. In Cell death discovery, 10, 290. doi:10.1038/s41420-024-02062-8. https://pubmed.ncbi.nlm.nih.gov/38886344/

5. Yong, Xin, Hu, Wenfeng, Zhou, Xue, Burstein, Ezra, Jia, Da. 2018. Expression and purification of the SNX1/SNX6 complex. In Protein expression and purification, 151, 93-98. doi:10.1016/j.pep.2018.06.010. https://pubmed.ncbi.nlm.nih.gov/29908913/