A trimeric CrRLK1L-LLG1 complex genetically modulates SUMM2-mediated autoimmunity

Julia Richter,Baomin Feng,Dongdong Ge,Ping He,Libo Shan,Chuanchun Yin,Yanyan Huang,Marie-Theres Hauser,Jun Liu,Fausto Andres Ortiz-Morea,Liang Kong,Wen-Ming Wang

doi:10.1038/s41467-020-18600-8

Abstract

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.

Highlights

Cell death is intrinsically linked with immunity
Two mutants, SALK_139579 and SALK_066322, but not the other 13 mutants of 12 Catharanthus roseus receptor-like kinase 1-like (CrRLK1L), suppressed the growth defects and cell death caused by RNAi-MEKK1 (Fig. 1b, c and Supplementary Fig. 1b)
Similar with LET1, LET2/MDS1 acts genetically downstream of MEKK2 and upstream of SUPPRESSOR OF mkk1 mkk2 (SUMM2) (Fig. 3)

Summary

Introduction

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. 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-mpk[4] cell death. 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-mpk[4] cell death pathway. 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. RLKs with an extracellular malectin-like domain, called Catharanthus roseus RLK1-like kinases (CrRLK1Ls), have long been known to be key regulators in various developmental processes including cell elongation, polarized growth, and fertilization[12,13,14,15]

Methods

Results

Conclusion