A trimeric CrRLK1L-LLG1 complex genetically modulates SUMM2-mediated autoimmunity. Academic Article uri icon


  • 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.

published proceedings

  • Nat Commun

altmetric score

  • 12.7

author list (cited authors)

  • Huang, Y., Yin, C., Liu, J., Feng, B., Ge, D., Kong, L., ... He, P.

citation count

  • 20

complete list of authors

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

publication date

  • January 2020