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A trimeric Cr RLK1L-LLG1 complex genetically modulates SUMM2-mediated autoimmunity
Nature Communications ( IF 16.6 ) Pub Date : 2020-09-25 , DOI: 10.1038/s41467-020-18600-8
Yanyan Huang , Chuanchun Yin , Jun Liu , Baomin Feng , Dongdong Ge , Liang Kong , Fausto Andres Ortiz-Morea , Julia Richter , Marie-Theres Hauser , Wen-Ming Wang , Libo Shan , Ping He

Cell death is intrinsically linked with immunity. Disruption of an immune-activated MAPK cascade, consisting of MEKK1, MKK1/2, and MPK4, triggers cell death and autoimmunity through the nucleotide-binding leucine-rich repeat (NLR) protein SUMM2 and the MAPK kinase kinase MEKK2. In this study, we identify a Catharanthus roseus receptor-like kinase 1-like (CrRLK1L), named LETUM2/MEDOS1 (LET2/MDS1), and the glycosylphosphatidylinositol (GPI)-anchored protein LLG1 as regulators of mekk1-mkk1/2-mpk4 cell death. LET2/MDS1 functions additively with LET1, another CrRLK1L, and acts genetically downstream of MEKK2 in regulating SUMM2 activation. LET2/MDS1 complexes with LET1 and promotes LET1 phosphorylation, revealing an intertwined regulation between different CrRLK1Ls. LLG1 interacts with the ectodomain of LET1/2 and mediates LET1/2 transport to the plasma membrane, corroborating its function as a co-receptor of LET1/2 in the mekk1-mkk1/2-mpk4 cell death pathway. Thus, our data suggest that a trimeric complex consisting of two CrRLK1Ls LET1, LET2/MDS1, and a GPI-anchored protein LLG1 that regulates the activation of NLR SUMM2 for initiating cell death and autoimmunity.



中文翻译:

三聚体Cr RLK1L-LLG1复合物基因调节SUMM2介导的自身免疫

细胞死亡与免疫有着内在的联系。由 MEKK1、MKK1/2 和 MPK4 组成的免疫激活 MAPK 级联的中断,通过核苷酸结合的富含亮氨酸重复序列 (NLR) 蛋白 SUMM2 和 MAPK 激酶激酶 MEKK2 触发细胞死亡和自身免疫。在这项研究中,我们确定了长春花受体样激酶 1 样 ( Cr RLK1L),命名为 LETUM2/MEDOS1 (LET2/MDS1),以及作为mekk1-mkk1/2调节剂的糖基磷脂酰肌醇 (GPI) 锚定蛋白 LLG1 - mpk4细胞死亡。LET2/MDS1 与 LET1(另一种CrRLK1L,并在 MEKK2 的遗传下游调节 SUMM2 激活。LET2/MDS1 与 LET1 复合并促进 LET1 磷酸化,揭示了不同Cr RLK1L之间相互交织的调节。LLG1 与 LET1/2 的胞外域相互作用并介导 LET1/2 向质膜的转运,证实其在mekk1-mkk1/2 - mpk4细胞死亡途径中作为 LET1/2 共同受体的功能。因此,我们的数据表明,由两个Cr RLK1Ls LET1、LET2/MDS1 和一个 GPI 锚定蛋白 LLG1组成的三聚体复合物调节 NLR SUMM2 的激活以启动细胞死亡和自身免疫。

更新日期:2020-09-25
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