title: Peptidoglycan recognition protein-S5 functions as a negative regulator of the antimicrobial peptide pathway in the silkworm, Bombyx mori.
abstract: Prophenoloxidase (proPO), immune deficiency (IMD), and Toll are the major signaling pathways leading to melanization and antimicrobial peptide production in insect hemolymph. Peptidoglycan recognition proteins (PGRPs) act as receptors and negative regulators in these pathways, and some PGRPs exhibit antimicrobial activity. Previously, we demonstrated that silkworm PGRP-S5 recognizes peptidoglycans (PGs) and triggers activation of the proPO pathway. It also acts as a bactericide, via its amidase activity (Chen et al., 2014). Here, we generated a C177S site-mutated silkworm PGRP-S5 protein that lacked amidase activity but retained its PG-binding capacity. Functional studies showed that the mutation caused loss of its receptor function for activation of the proPO pathway, suggesting that processing of PG by PGRP-S5 is necessary for formation of the pathway initiation complex. Further, we found that PGRP-S5 negatively regulates antimicrobial peptides generation in an amidase-dependent manner, likely through the IMD pathway. Thus, silkworm PGRP-S5 acts as a sensor, a modulator, and an effector in the silkworm humoral immune system.
authors.affiliation: Department of Entomology, College of Plant Protection, Northwest A&F University, Yangling, Shaanxi 712100, China.
authors.forename: Kangkang
authors.initials: K
authors.lastname: Chen
authors.affiliation: Department of Entomology, College of Plant Protection, Northwest A&F University, Yangling, Shaanxi 712100, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of Entomology, College of Plant Protection, Northwest A&F University, Yangling, Shaanxi 712100, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Chen
authors.affiliation: Department of Entomology, College of Plant Protection, Northwest A&F University, Yangling, Shaanxi 712100, China.
authors.forename: Yachun
authors.initials: Y
authors.lastname: Peng
authors.affiliation: Department of Entomology, College of Plant Protection, Northwest A&F University, Yangling, Shaanxi 712100, China. Electronic address: zhiqiang.lu@nwsuaf.edu.cn.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Lu
mesh_terms: D000581:Amidohydrolases / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000890:Anti-Infective Agents / Q000378:metabolism*; D012831:Bombyx / Q000276:immunology*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D004156:Catechol Oxidase / Q000378:metabolism; D002478:Cells, Cultured; D004792:Enzyme Precursors / Q000378:metabolism; D006458:Hemolymph / Q000378:metabolism; D056724:Immunity, Humoral; D007113:Immunity, Innate; D019476:Insect Proteins / Q000378:metabolism*; D008543:Melanins / Q000378:metabolism; D016297:Mutagenesis, Site-Directed; D009154:Mutation / Q000235:genetics; D010455:Peptides / Q000378:metabolism*; D010457:Peptidoglycan / Q000276:immunology; D015398:Signal Transduction
chemical_list: D000890:Anti-Infective Agents; D002352:Carrier Proteins; D004792:Enzyme Precursors; D019476:Insect Proteins; D008543:Melanins; D010455:Peptides; D010457:Peptidoglycan; C118897:peptidoglycan recognition protein; C038451:pro-phenoloxidase; D004156:Catechol Oxidase; D000581:Amidohydrolases; C019665:amidase
keywords: Antimicrobial peptide; Bombyx mori; Immune; Peptidoglycan recognition proteins; Prophenoloxidase