TY - JOUR
T1 - Peptidoglycan recognition in Drosophila is mediated by LysMD3/4
AU - Snee, Mark
AU - Wever, Jason
AU - Guyton, Jennifer
AU - Beehler-Evans, Ryan
AU - Yokoyama, Christine C.
AU - Micchelli, Craig A.
N1 - Funding Information:
This research was supported by the National Institute of Health ( R01 DK 108990 , R01 DK117335 to C. A. M). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Funding Information:
We thank Bloomington Drosophila Stock Center, Developmental Studies Hybridoma Bank, and Washington University Center for Cellular Imaging for resources that facilitated this study. M. S. J. W. J. G. R. B.-E. C. C. Y. and C. A. M. conceptualization; M. S. J. W. J. G. R. B.-E. and C. A. M. investigation; M. S. J. W. J. G. and R. B.-E. formal analysis; M. S. and C. A. M. writing–original draft. This research was supported by the National Institute of Health (R01 DK 108990, R01 DK117335 to C. A. M). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Publisher Copyright:
© 2023 The Authors
PY - 2023/6
Y1 - 2023/6
N2 - Microbial recognition is a key step in regulating the immune signaling pathways of multicellular organisms. Peptidoglycan, a component of the bacterial cell wall, exhibits immune stimulating activity in both plants and animals. Lysin motif domain (LysMD) family proteins are ancient peptidoglycan receptors that function in bacteriophage and plants. This report focuses on defining the role of LysMD-containing proteins in animals. Here, we characterize a novel transmembrane LysMD family protein. Loss-of-function mutations at the lysMD3/4 locus in Drosophila are associated with systemic innate immune activation following challenge, so we refer to this gene as immune active (ima). We show that Ima selectively binds peptidoglycan, is enriched in cell membranes, and is necessary to regulate terminal innate immune effectors through an NF-kB–dependent pathway. Hence, Ima fulfills the key criteria of a peptidoglycan pattern recognition receptor. The human Ima ortholog, hLysMD3, exhibits similar biochemical properties. Together, these findings establish LysMD3/4 as the founding member of a novel family of animal peptidoglycan recognition proteins.
AB - Microbial recognition is a key step in regulating the immune signaling pathways of multicellular organisms. Peptidoglycan, a component of the bacterial cell wall, exhibits immune stimulating activity in both plants and animals. Lysin motif domain (LysMD) family proteins are ancient peptidoglycan receptors that function in bacteriophage and plants. This report focuses on defining the role of LysMD-containing proteins in animals. Here, we characterize a novel transmembrane LysMD family protein. Loss-of-function mutations at the lysMD3/4 locus in Drosophila are associated with systemic innate immune activation following challenge, so we refer to this gene as immune active (ima). We show that Ima selectively binds peptidoglycan, is enriched in cell membranes, and is necessary to regulate terminal innate immune effectors through an NF-kB–dependent pathway. Hence, Ima fulfills the key criteria of a peptidoglycan pattern recognition receptor. The human Ima ortholog, hLysMD3, exhibits similar biochemical properties. Together, these findings establish LysMD3/4 as the founding member of a novel family of animal peptidoglycan recognition proteins.
KW - Drosophila
KW - NF-kappa B
KW - human
KW - innate immunity
KW - lysin motif domain
KW - pattern recognition receptor
KW - peptidoglycan
UR - http://www.scopus.com/inward/record.url?scp=85160406728&partnerID=8YFLogxK
U2 - 10.1016/j.jbc.2023.104758
DO - 10.1016/j.jbc.2023.104758
M3 - Article
C2 - 37116706
AN - SCOPUS:85160406728
SN - 0021-9258
VL - 299
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 6
M1 - 104758
ER -