A family of peptidoglycan recognition proteins in the fruit flyDrosophila melanogaster

Abstract

Peptidoglycans from bacterial cell walls trigger immune responses in insects and mammals. A peptidoglycan recognition protein, PGRP, has been cloned from moths as well as vertebrates and has been shown to participate in peptidoglycan-mediated activation of prophenoloxidase in the silk moth. Here we report that Drosophila expresses 12 PGRP genes, distributed in 8 chromosomal loci on the 3 major chromosomes. By analyzing cDNA clones and genomic databases, we grouped them into two classes: PGRP-SA, SB1, SB2, SC1A, SC1B, SC2, and SD, with short transcripts and short 5-untranslated regions; and PGRP-LA, LB, LC, LD, and LE, with long transcripts and long 5-untranslated regions. The predicted structures indicate that the first group encodes extracellular proteins and the second group, intracellular and membrane-spanning proteins. Most PGRP genes are expressed in all postembryonic stages. Peptidoglycan injections strongly induce five of the genes. Transcripts from the different PGRP genes were found in immune competent organs such as fat body, gut, and hemocytes. We demonstrate that at least PGRP-SA and SC1B can bind peptidoglycan, and a function in immunity is likely for this family.

Drosophila Toll is activated by Gram-positive bacteria through a circulating peptidoglycan recognition protein

“…The deduced sequence of the PGRP-SA gene indicates the presence of a putative signal peptide 18 , suggesting that the PGRP-SA protein is a secreted protein present in the haemolymph or possibly associated with the extracellular matrix. We reasoned that if the PGRP-SA protein is present in the haemolymph, we should be able to rescue the seml phenotype by transferring wild-type haemolymph into the mutant¯ies.…”

Expression and functional characterization of PGRP6 splice variants in grass carp Ctenopharyngodon idella

“…PGRP-LCa, PGRP-LCx and PGRP-LCy, are generated by alternative splicing; they share common cytoplasmic and transmembrane domains. However, each variant of PGRP-LC has a separate extracellular PGRP domain (x, y or a), and the extracellular PGRP domains are only 39% identical (Choe et al, 2002;Kaneko et al, 2004;Werner et al, 2000Werner et al, , 2003. In mouse, TagL (PGRP-L) has six splicing variants (TagL-α, TagL-β, TagL-γ, TagL-δ, TagL-ε and TagL-μ), which are all identical in the N-terminal portion.…”

“…In mammals, the members of Toll-like receptors (TLRs), nucleotide oligomerization domain-like receptors (NLRs) and peptidoglycan recognition proteins (PGRPs) families mediate PGN recognition (Girardin and Philpott, 2004;Takeuchi et al, 1999). Among which, PGRPs are ubiquitous and conserved through evolution, and present in most invertebrates such as insects (Werner et al, 2000), mollusks Su et al, 2007) and echinoderms (Coteur et al, 2007), as well as in all vertebrate animals (Kang et al, 1998;Liu et al, 2001). …”

“…Insects have many PGRP genes; for example, Drosophila melanogaster has 13 PGRP genes (Werner et al, 2000), and seven PGRP genes are present in mosquito Anopheles gambiae (Christophides et al, 2002). However, vertebrates have a smaller number of PGRP genes; four genes including PGLYRP-1, PGLYRP-2, PGLYRP-3 and PGLYRP-4 exist in mammals (Liu et al, 2001) and three PGRPs including PGLYRP-2 (PGRP2), PGLYRP-5 (PGRP5) and PGLYRP-6 (PGRP6) in teleost fish Li et al, 2007).…”

Gene transfer approaches in cancer immunotherapy

“…71 It was designated tagL because it encodes the protein almost twice larger than Tag7/PGRP-S. Later, a large family of genes was identified in Drosophila and human genomes using the same approach. 72,73 Mammalian Tag7/PGRP-S has been cloned from mouse, 69 human, 70 rat, 74 and cow. 75 There are small extracellular proteins (19)(20)(21)(22)(23)(24), which structurally share homology with T phage lyzozyme but do not possess any amidaze activity.…”