LMBR1L regulates lymphopoiesis through Wnt/?-catenin signaling.
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/?-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/?-catenin pathway.
Mesh Terms:
Animals, HEK293 Cells, Humans, Lymphopoiesis, Mice, Inbred C57BL, Mice, Mutant Strains, Receptors, Cell Surface, Wnt Proteins, Wnt Signaling Pathway, beta Catenin
Animals, HEK293 Cells, Humans, Lymphopoiesis, Mice, Inbred C57BL, Mice, Mutant Strains, Receptors, Cell Surface, Wnt Proteins, Wnt Signaling Pathway, beta Catenin
Science
Date: Dec. 10, 2018
PubMed ID: 31073040
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