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LMBR1Lは,Wnt/β-cateninシグナル伝達を通じてリンパポエーシスを調節する

Jin Huk Choi¹, Xue Zhong¹, William McAlpine¹

¹Center for the Genetics of Host Defense, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.

Science (New York, N.Y.)

|May 11, 2019

まとめ

末端領域1型遺伝子 (Lmbr1l) の変異は,Wnt信号調節を妨害することで免疫細胞の発達を阻害する. Lmbr1l欠乏症はT細胞の欠陥とアポトーシスを引き起こし,リンパ系形成における重要な役割を強調する.

科学分野:

免疫学
分子生物学
遺伝学

背景:

Wnt信号の正確な調節は,適切な免疫システムの発達に不可欠です.
肢領域1型遺伝子 (Lmbr1l) は,免疫における役割が不明の膜タンパク質をコードする.

研究の目的:

免疫系の発達における Lmbr1l の機能を調査する.
リンパ球におけるWnt信号伝達をLmbr1lが調節するメカニズムを解明する.

主な方法:

N-エチル-N-ニトロ尿素を用いたマウスの変異誘導で,リンパ球発達の影響を及ぼす遺伝子を特定した.
Lmbr1l変異マウスのリンパ系発達の分析
タンパク質の相互作用 (LMBR1L,GP78,UBAC2) と,Wnt経路の成分 (FZD6,LRP6) に対するその影響の調査.
Lmbr1l欠乏細胞におけるT細胞アポトーシスとWnt/β-カタニン経路活性化の評価

主要な成果:

Lmbr1lの変異は,マウスのリンパ系全体の発達に重大な障害をもたらした.
LMBR1LはGP78とUBAC2と相互作用し,FZD6とLRP6の成熟を防止し,破壊複合体のタンパク質を安定させます.
LMBR1L欠乏性T細胞は,Wnt/β-カテニンの活性化の特徴を示し,増殖刺激によってアポトーシスを経験した.

結論:

LMBR1Lはリンパポエーゼとリンパ球の活性化に不可欠です.
LMBR1Lは,免疫系におけるWnt/β-カテニンの経路の負の調節剤として機能する.

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