Yang Wenwen, Sun Jiejie, Guo Qiuyan, Wang Wei, Leng Jinyuan, Wang Lingling, Song Linsheng
Liaoning Key Laboratory of Marine Animal Immunology, Dalian Ocean University, 52 Heishijiao Street, Dalian, 116023, China.
Liaoning Key Laboratory of Marine Animal Immunology & Disease Control, Dalian Ocean University, Dalian, 116023, China.
Cell Commun Signal. 2025 Feb 25;23(1):110. doi: 10.1186/s12964-025-02111-4.
The leucine rich repeat and sterile alpha motif containing 1 (LRSAM1) as E3 ligase recognizes bacteria and generates a ubiquitin signal to initiate the autophagy process. In the present study, LRSAM1 was identified from the Pacific oyster Crassostrea gigas (designed as CgLRSAM1), which was able to recognize various pathogen-associated molecular patterns and bacteria and directly ubiquitinate Vibrio splendidus. V. splendidus was co-localized with CgLRSAM1 and ubiquitin after invading haemocytes, and the ubiquitinated V. splendidus was then internalized into haemocyte lysosomes by p62-LC3-mediated autophagy. In haemocytes of CgLRSAM1-RNAi oysters, the activation of CgLC3 was enhanced after V. splendidus stimulation. While the co-localization values of V. splendidus with ubiquitin, CgLC3 and lysosomes all decreased significantly after V. splendidus stimulation. These results indicated that CgLRSAM1 functioned as E3 ligase responsible for anti-Vibrio-associated ubiquitination and regulated the degradation of bacteria through the ubiquitination-autophagy-lysosome pathway.
富含亮氨酸重复序列和无活性α基序的蛋白1（LRSAM1）作为E3连接酶识别细菌并产生泛素信号以启动自噬过程。在本研究中，从太平洋牡蛎（Crassostrea gigas）中鉴定出LRSAM1（命名为CgLRSAM1），它能够识别各种病原体相关分子模式和细菌，并直接将灿烂弧菌泛素化。灿烂弧菌侵入血细胞后与CgLRSAM1和泛素共定位，然后通过p62-LC3介导的自噬将泛素化的灿烂弧菌内化到血细胞溶酶体中。在CgLRSAM1-RNAi牡蛎的血细胞中，灿烂弧菌刺激后CgLC3的激活增强。而灿烂弧菌刺激后，灿烂弧菌与泛素、CgLC3和溶酶体的共定位值均显著降低。这些结果表明，CgLRSAM1作为负责抗灿烂弧菌相关泛素化的E3连接酶，并通过泛素化-自噬-溶酶体途径调节细菌的降解。
