Modulation of Caenorhabditis elegans infection sensitivity by the LIN-7 cell junction protein.
In Caenorhabditis elegans, the LIN-2/7/10 protein complex regulates the activity of signalling proteins. We found that inhibiting lin-7 function, and also lin-2 and lin-10, resulted in enhanced C. elegans survival after infection by Burkholderia spp., implicating a novel role for these genes in modulating infection outcomes. Genetic experiments suggested that this infection phenotype is likely caused by modulation of the DAF-2 insulin/IGF-1 signalling pathway. Supporting these observations, yeast two-hybrid assays confirmed that the LIN-2 PDZ domain can physically bind to the DAF-2 C-terminus. Loss of lin-7 activity also altered DAF-16 nuclear localization kinetics, indicating an additional contribution by hsf-1. Unexpectedly, silencing lin-7 in the hypodermis, but not the intestine, was protective against infection, implicating the hypodermis as a key tissue in this phenomenon. Finally, consistent with lin-7 acting as a general host infection factor, lin-7 mutants also exhibited enhanced survival upon infection by two other Gram-negative pathogens, Pseudomonas and Salmonella spp.
Genome Institute of Singapore, Singapore, Singapore.
Xiaohui
X
Sem
Jason F
JF
Kreisberg
Trupti
T
Kawli
Man-Wah
MW
Tan
Mikael
M
Rhen
Patrick
P
Tan
D000818:Animals; D019117:Burkholderia / Q000472:pathogenicity; D017173:Caenorhabditis elegans / Q000276:immunology / Q000382:microbiology* / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D051858:Forkhead Transcription Factors; D017353:Gene Deletion; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D025941:Protein Interaction Mapping; D011549:Pseudomonas / Q000472:pathogenicity; D011972:Receptor, Insulin / Q000378:metabolism; D012475:Salmonella / Q000472:pathogenicity; D016019:Survival Analysis; D014157:Transcription Factors / Q000378:metabolism; D020798:Two-Hybrid System Techniques
D029742:Caenorhabditis elegans Proteins; D051858:Forkhead Transcription Factors; C099173:LIN-7 protein, C elegans; D008565:Membrane Proteins; D014157:Transcription Factors; C108831:daf-16 protein, C elegans; C107483:DAF-2 protein, C elegans; D011972:Receptor, Insulin