Drosophila peptidoglycan recognition protein LC (PGRP-LC) acts as a signal-transducing innate immune receptor.
Drosophila peptidoglycan recognition protein LC (PGRP-LC), a transmembrane protein required for the response to bacterial infection, acts at the top of a cytoplasmic signaling cascade that requires the death-domain protein Imd and an IkappaB kinase to activate Relish, an NF-kappaB family member. It is not clear how binding of peptidoglycan to the extracellular domain of PGRP-LC activates intracellular signaling because its cytoplasmic domain has no homology to characterized proteins. Here, we demonstrate that PGRP-LC binds Imd and that its cytoplasmic domain is critical for its activity, suggesting that PGRP-LC acts as a signal-transducing receptor. The PGRP-LC cytoplasmic domain is also essential for the formation of dimers, and results suggest that dimerization may be required for receptor activation. The PGRP-LC cytoplasmic domain can mediate formation of heterodimers between different PGRP-LC isoforms, thereby potentially expanding the diversity of ligands that can be recognized by the receptor.
Choe
Kwang-Min
KM
Developmental Biology Program, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA.
Lee
Hyangkyu
H
Anderson
Kathryn V
KV
D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry / Q000502:physiology*; D019281:Dimerization; D004330:Drosophila / Q000276:immunology*; D029721:Drosophila Proteins / Q000737:chemistry / Q000502:physiology; D007113:Immunity, Innate; D015398:Signal Transduction
D002352:Carrier Proteins; D029721:Drosophila Proteins; C439909:imd protein, Drosophila; C118897:peptidoglycan recognition protein