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 L 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 A Beutler

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article numbereaau0812
JournalScience
Volume364
Issue number6440
DOIs
StatePublished - Jan 1 2019

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Lymphopoiesis
Catenins
Wnt2 Protein
Ethylnitrosourea
Wnt Signaling Pathway
Ubiquitination
Ubiquitin
Endoplasmic Reticulum
Immune System
Immunity
Glycoproteins
Membrane Proteins
Cell Death
Extremities
Lymphocytes
T-Lymphocytes
Mutation
Genes
Proteins
Protein Domains

ASJC Scopus subject areas

  • General

Cite this

Choi, J. H., Zhong, X., McAlpine, W., Liao, T. C., Zhang Ph.D., D-W., Fang, B., ... Beutler, B. A. (2019). LMBR1L regulates lymphopoiesis through Wnt/β-catenin signaling. Science, 364(6440), [eaau0812]. https://doi.org/10.1126/science.aau0812

LMBR1L regulates lymphopoiesis through Wnt/β-catenin signaling. / Choi, Jin Huk; Zhong, Xue; McAlpine, William; Liao, Tzu Chieh; Zhang Ph.D., Duan-Wu; Fang, Beibei; Russell, Jamie L; Ludwig, Sara; Nair-Gill, Evan; Zhang, Zhao; Wang, Kuan Wen; Misawa, Takuma; Zhan, Xiaoming; Choi, Mihwa; Wang, Tao; Li, Xiaohong; Tang, Miao; Sun, Qihua; Yu, Liyang; Murray, Anne R.; Moresco, Evamarie Y.; Beutler, Bruce A.

In: Science, Vol. 364, No. 6440, eaau0812, 01.01.2019.

Research output: Contribution to journalArticle

Choi, JH, Zhong, X, McAlpine, W, Liao, TC, Zhang Ph.D., D-W, Fang, B, Russell, JL, Ludwig, S, Nair-Gill, E, Zhang, Z, Wang, KW, Misawa, T, Zhan, X, Choi, M, Wang, T, Li, X, Tang, M, Sun, Q, Yu, L, Murray, AR, Moresco, EY & Beutler, BA 2019, 'LMBR1L regulates lymphopoiesis through Wnt/β-catenin signaling', Science, vol. 364, no. 6440, eaau0812. https://doi.org/10.1126/science.aau0812
Choi JH, Zhong X, McAlpine W, Liao TC, Zhang Ph.D. D-W, Fang B et al. LMBR1L regulates lymphopoiesis through Wnt/β-catenin signaling. Science. 2019 Jan 1;364(6440). eaau0812. https://doi.org/10.1126/science.aau0812
Choi, Jin Huk ; Zhong, Xue ; McAlpine, William ; Liao, Tzu Chieh ; Zhang Ph.D., Duan-Wu ; Fang, Beibei ; Russell, Jamie L ; Ludwig, Sara ; Nair-Gill, Evan ; Zhang, Zhao ; Wang, Kuan Wen ; Misawa, Takuma ; Zhan, Xiaoming ; Choi, Mihwa ; Wang, Tao ; Li, Xiaohong ; Tang, Miao ; Sun, Qihua ; Yu, Liyang ; Murray, Anne R. ; Moresco, Evamarie Y. ; Beutler, Bruce A. / LMBR1L regulates lymphopoiesis through Wnt/β-catenin signaling. In: Science. 2019 ; Vol. 364, No. 6440.
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AU - Zhang Ph.D., Duan-Wu

AU - Fang, Beibei

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AU - Nair-Gill, Evan

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AU - Wang, Kuan Wen

AU - Misawa, Takuma

AU - Zhan, Xiaoming

AU - Choi, Mihwa

AU - Wang, Tao

AU - Li, Xiaohong

AU - Tang, Miao

AU - Sun, Qihua

AU - Yu, Liyang

AU - Murray, Anne R.

AU - Moresco, Evamarie Y.

AU - Beutler, Bruce A

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