LMBR1L regulates lymphopoiesis through Wnt/β-catenin signaling

Jin Huk Choi; Xue Zhong; William McAlpine; Tzu Chieh Liao; Duanwu Zhang; 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. Murray; Evamarie Y. Moresco; Bruce Beutler

doi:10.1126/science.aau0812

LMBR1L regulates lymphopoiesis through Wnt/β-catenin signaling

Jin Huk Choi, Xue Zhong, William McAlpine, Tzu Chieh Liao, Duanwu Zhang, 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

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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 language	English (US)
Article number	eaau0812
Journal	Science
Volume	364
Issue number	6440
DOIs	https://doi.org/10.1126/science.aau0812
State	Published - 2019

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Choi, J. H., 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., ... Beutler, B. (2019). LMBR1L regulates lymphopoiesis through Wnt/β-catenin signaling. Science, 364(6440), Article eaau0812. https://doi.org/10.1126/science.aau0812

Choi, JH , Zhong, X, McAlpine, W, Liao, TC, Zhang, D, Fang, B, Russell, J , 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, B 2019, 'LMBR1L regulates lymphopoiesis through Wnt/β-catenin signaling', Science, vol. 364, no. 6440, eaau0812. https://doi.org/10.1126/science.aau0812

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title = "LMBR1L regulates lymphopoiesis through Wnt/β-catenin signaling",

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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year = "2019",

doi = "10.1126/science.aau0812",

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AU - Choi, Jin Huk

AU - Zhong, Xue

AU - McAlpine, William

AU - Liao, Tzu Chieh

AU - Zhang, Duanwu

AU - Fang, Beibei

AU - Russell, Jamie

AU - Ludwig, Sara

AU - Nair-Gill, Evan

AU - Zhang, Zhao

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

PY - 2019

Y1 - 2019

N2 - 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.

AB - 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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LMBR1L regulates lymphopoiesis through Wnt/β-catenin signaling

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