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在C. elegans的发育过程中,托尔类受体与拉特罗菲林结合的结构基础和功能作用

Gabriel Carmona-Rosas^1,2,3, Jingxian Li^1,2,3, Jayson J Smith^2,4

¹Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, IL, USA.

Nature structural & molecular biology

|June 30, 2025

概括

收费类受体1 (TOL-1) 与G蛋白结合受体拉托菲林1 (LAT-1) 结合,揭示了C. elegans胚胎发育的关键相互作用. 这种受体-连接体轴对于预防胚胎缺陷和致死性至关重要.

科学领域:

发育生物学发展生物学
分子生物学分子生物学
结构生物学结构生物学

背景情况:

拉特罗菲林是保存的G蛋白结合受体,参与胚胎发育.
拉特罗菲林在胚胎发生过程中的特定连接体和机械作用在很大程度上是未知的.

研究的目的:

为了识别Caenorhabditis elegans latrophilin,LAT-1的连接体,可以使用LAT-1.
阐明LAT-1-联体相互作用在胚胎发育中的结构基础和功能意义.

主要方法:

确定了TOL-1作为C. elegans中LAT-1的唯一的Toll类受体连接体.
确定了LAT-1-TOL-1细胞外复合体的晶体结构和冷电子显微镜密度图.
进行了突变性研究以破坏LAT-1-TOL-1相互作用,并分析了胚胎表型.

主要成果:

LAT-1的细胞外莱克域直接与TOL-1的富含白的重复域结合,进行一对一的相互作用.
LAT-1和TOL-1表现出相互排斥的表达模式,这表明在体内发生过渡相互作用.
破坏LAT-1-TOL-1相互作用导致部分致死性和发育不良的胚胎.

结论:

在C. elegans中,TOL-1是LAT-1的直接连接体.
LAT-1-TOL-1受体-连接体轴对于正常的胚胎发育至关重要,防止致命性和形.

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