LMBR1L regulates lymphopoiesis through Wnt/β-catenin signaling.
Jin Huk ChoiXue ZhongWilliam McAlpineTzu-Chieh LiaoDuanwu ZhangBeibei FangJamie RussellSara LudwigEvan Nair-GillZhao ZhangKuan-Wen WangTakuma MisawaXiaoming ZhanMihwa ChoiTao WangXiaohong LiMiao TangQihua SunLiyang YuAnne R MurrayEva Marie Y MorescoBruce A BeutlerPublished in: Science (New York, N.Y.) (2019)
Precise control of Wnt signaling is necessary for immune system development. In this study, we detected severely impaired development of all lymphoid lineages in mice, resulting from an N-ethyl-N-nitrosourea-induced mutation in the limb region 1-like gene (Lmbr1l), which encodes a membrane-spanning protein with no previously described function in immunity. The interaction of LMBR1L with glycoprotein 78 (GP78) and ubiquitin-associated domain-containing protein 2 (UBAC2) attenuated Wnt signaling in lymphocytes by preventing the maturation of FZD6 and LRP6 through ubiquitination within the endoplasmic reticulum and by stabilizing "destruction complex" proteins. LMBR1L-deficient T cells exhibited hallmarks of Wnt/β-catenin activation and underwent apoptotic cell death in response to proliferative stimuli. LMBR1L has an essential function during lymphopoiesis and lymphoid activation, acting as a negative regulator of the Wnt/β-catenin pathway.
Keyphrases
- cell death
- cell proliferation
- endoplasmic reticulum
- stem cells
- protein protein
- amino acid
- binding protein
- epithelial mesenchymal transition
- peripheral blood
- transcription factor
- high fat diet induced
- wild type
- dna methylation
- ionic liquid
- metabolic syndrome
- endothelial cells
- pi k akt
- skeletal muscle
- insulin resistance
- stress induced