2. Academic Validation
  3. LMBR1L regulates lymphopoiesis through Wnt/β-catenin signaling

LMBR1L regulates lymphopoiesis through Wnt/β-catenin signaling

  • Science. 2019 May 10;364(6440):eaau0812. doi: 10.1126/science.aau0812.
Jin Huk Choi # 1,  Xue Zhong # 1,  William McAlpine 1,  Tzu-Chieh Liao 1,  Duanwu Zhang 1,  Beibei Fang 1,  Jamie Russell 1,  Sara Ludwig 1,  Evan Nair-Gill 1,  Zhao Zhang 1,  Kuan-Wen Wang 1,  Takuma Misawa 1,  Xiaoming Zhan 1,  Mihwa Choi 1,  Tao Wang 1 2,  Xiaohong Li 1,  Miao Tang 1,  Qihua Sun 1,  Liyang Yu 1,  Anne R Murray 1,  Eva Marie Y Moresco 1,  Bruce Beutler 3
Affiliations

Affiliations

  • 1 Center for the Genetics of Host Defense, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
  • 2 Quantitative Biomedical Research Center, Department of Clinical Science, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
  • 3 Center for the Genetics of Host Defense, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. [email protected].
  • # Contributed equally.
PMID: 31073040 DOI: 10.1126/science.aau0812
Abstract

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.

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