M6pr-KO Mouse

M6pr, also known as the mannose-6-phosphate receptor, exists in two forms: cation-independent (CI-M6PR) and cation-dependent (CD-M6PR). It plays a crucial role in coordinating the targeting of lysosomal enzymes to lysosomes, a process essential for maintaining normal lysosomal function [1]. The M6P-dependent trafficking pathway, in which M6pr is involved, is associated with lysosomal reformation and autophagy-lysosomal function [1].

Mutations in CLN3, a gene related to Batten disease, lead to mis-trafficking of CI-M6PR, mis-sorting of lysosomal enzymes, and defective autophagic lysosomal reformation [1]. In esophageal cancer, exosomal M6PR promotes tumor angiogenesis, and high serum M6PR levels are associated with poor overall survival [2]. M6PR also interacts with the HA2 subunit of influenza A virus to facilitate the fusion of viral and endosomal membranes [3]. In respiratory syncytial virus (RSV) infection, Gimap5 promotes RSV degradation by interacting with M6PR [4].

In conclusion, M6pr is essential for lysosomal enzyme targeting and the proper functioning of lysosomal-related pathways. Studies on M6pr in disease models, such as in Batten disease, esophageal cancer, influenza A virus, and RSV infection, have revealed its significance in disease-related processes. Understanding M6pr's functions provides insights into the mechanisms of these diseases and may offer potential therapeutic targets.

References:

1. Calcagni', Alessia, Staiano, Leopoldo, Zampelli, Nicolina, Grumati, Paolo, Ballabio, Andrea. 2023. Loss of the batten disease protein CLN3 leads to mis-trafficking of M6PR and defective autophagic-lysosomal reformation. In Nature communications, 14, 3911. doi:10.1038/s41467-023-39643-7. https://pubmed.ncbi.nlm.nih.gov/37400440/

2. Yan, Dongdong, Cui, Di, Zhu, Yun, Ma, Stephanie, Cheung, Annie Lai Man. 2023. M6PR- and EphB4-Rich Exosomes Secreted by Serglycin-Overexpressing Esophageal Cancer Cells Promote Cancer Progression. In International journal of biological sciences, 19, 625-640. doi:10.7150/ijbs.79875. https://pubmed.ncbi.nlm.nih.gov/36632458/

3. Hu, Yuzhen, Jiang, Li, Wang, Guangwen, Chen, Hualan, Li, Chengjun. 2023. M6PR interacts with the HA2 subunit of influenza A virus to facilitate the fusion of viral and endosomal membranes. In Science China. Life sciences, 67, 579-595. doi:10.1007/s11427-023-2471-4. https://pubmed.ncbi.nlm.nih.gov/38038885/

4. Dai, Pei, Ruan, Pinglang, Mao, Yu, Bajinka, Ousman, Tan, Yurong. . Gimap5 promoted RSV degradation through interaction with M6PR. In Journal of medical virology, 95, e28390. doi:10.1002/jmv.28390. https://pubmed.ncbi.nlm.nih.gov/36484389/