LMBR1L regulates lymphopoiesis through Wnt/β-catenin signaling.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Choi, JH; Zhong, X; McAlpine, W; Liao, T-C; Zhang, D; Fang, B; Russell, J; Ludwig, S; Nair-Gill, E; Zhang, Z; Wang, K-W; Misawa, T; Zhan, X; Choi, M; Wang, T; Li, X; Tang, M; Sun, Q; Yu, L; Murray, AR; Moresco, EMY; Beutler, B

Published Date

  • May 2019

Published In

Volume / Issue

  • 364 / 6440

Start / End Page

  • eaau0812 -

PubMed ID

  • 31073040

Pubmed Central ID

  • PMC7206793

Electronic International Standard Serial Number (EISSN)

  • 1095-9203

International Standard Serial Number (ISSN)

  • 0036-8075

Digital Object Identifier (DOI)

  • 10.1126/science.aau0812

Language

  • eng