LMBR1L regulates lymphopoiesis through Wnt/β-catenin signaling

Jin Huk Choi, Xue Zhong, William McAlpine, Tzu Chieh Liao, Duan-Wu Zhang Ph.D., Beibei Fang, Jamie Russell, Sara Ludwig, Evan Nair-Gill, Zhao Zhang, Kuan Wen Wang, Takuma Misawa, Xiaoming Zhan, Mihwa Choi, Tao Wang, Xiaohong Li, Miao Tang, Qihua Sun, Liyang Yu, Anne R. MurrayEvamarie Y. Moresco, Bruce Beutler

Research output: Contribution to journalArticlepeer-review

31 Scopus citations


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.

Original languageEnglish (US)
Article numbereaau0812
Issue number6440
StatePublished - 2019

ASJC Scopus subject areas

  • General


Dive into the research topics of 'LMBR1L regulates lymphopoiesis through Wnt/β-catenin signaling'. Together they form a unique fingerprint.

Cite this