A receptor tyrosine kinase regulated by the transcription factor VAB-3/PAX6 pairs with a pseudokinase to trigger immune signalling upon oomycete recognition inC. elegans

Abstract

SummaryOomycetes were recently discovered as natural pathogens ofCaenorhabditis elegansand pathogen recognition alone was shown to be sufficient to activate a protective transcriptional program in the host characterised by the expression of multiplechitinase-like(chil) genes. However, the molecular mechanisms underlying oomycete recognition in animals remain fully unknown. We performed here a forward genetic screen to uncover regulators ofchilgene induction and found several independent loss-of-function alleles ofold-1andflor-1,which encode receptor tyrosine kinases belonging to theC. elegans-specific KIN-16 family. We present evidence that OLD-1 is an active kinase mounting the immune response, and FLOR-1 a pseudokinase that is also required for the response and regulates the distribution of OLD-1 at the epidermal membrane. Interestingly, theold-1locus is adjacent to thechilgenes in the nematode genome, thereby revealing a genetic cluster important for oomycete-resistance. Furthermore, we identify the VAB-3/PAX-6 transcription factor known for its role in visual system development to regulateold-1expression, and consequently the spatial pattern of the response to oomycete recognition. Taken together, our study reveals both conserved and species-specific factors shaping the response to oomycete recognition.