Proteolytic Cascade for the Activation of the Insect Toll Pathway Induced by the Fungal Cell Wall Component

Roh, Kyung‐Baeg; Kim, Chan-Hee; Lee, Hanna; Kwon, Hyuktae; Park, Ji Won; Ryu, Ji-Hwan; Kurokawa, Kenji; Ha, Nam‐Chul; Lee, Won–Jae; Lemaître, Bruno; Söderhäll, Kenneth; Lee, Bok Luel

doi:10.1074/jbc.m109.007419

Cited by 143 publications

(125 citation statements)

References 35 publications

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“…Tenecin-1, an AMP which is active specifically against Gram-positive bacteria, was first identified by purifying the peptide from a haemolymph fraction showing antimicrobial activity [19]. Tenecin-2 was identified simultaneously [20] and is active against Gram-negative bacteria. Tenecin-3 is antifungal [21], while Tenecin-4 is anti-Gram negative [22].…”

Section: Introductionmentioning

confidence: 99%

Antimicrobial defence and persistent infection in insects revisited

Makarova

Rodríguez‐Rojas

Eravci

et al. 2016

Phil. Trans. R. Soc. B

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One contribution of 13 to a theme issue 'Evolutionary ecology of arthropod antimicrobial peptides'. Insects show long-lasting antimicrobial immune responses that follow the initial fast-acting cellular processes. These immune responses are discussed to provide a form of phrophylaxis and/or to serve as a safety measure against persisting infections. The duration and components of such longlasting responses have rarely been studied in detail, a necessary prerequisite to understand their adaptive value. Here, we present a 21 day proteomic time course of the mealworm beetle Tenebrio molitor immune-challenged with heat-killed Staphylococcus aureus. The most upregulated peptides are antimicrobial peptides (AMPs), many of which are still highly abundant 21 days after infection. The identified AMPs included toll and imd-mediated AMPs, a significant number of which have no known function against S. aureus or other Gram-positive bacteria. The proteome reflects the selective arena for bacterial infections. The results also corroborate the notion of synergistic interactions in vivo that are difficult to model in vitro.This article is part of the themed issue 'Evolutionary ecology of arthropod antimicrobial peptides'.

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Section: Introductionmentioning

confidence: 99%

Antimicrobial defence and persistent infection in insects revisited

Makarova

Rodríguez‐Rojas

Eravci

et al. 2016

Phil. Trans. R. Soc. B

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“…2). These results suggest that SPN55 and SPN48 have the putative P2 Tyr and P1Ј Glu residues as the actual cleavage sites, respectively, despite the fact that the trypsin-like SAE and SPE were shown to be Arg-specific SPs in our previous studies (10,11).…”

Section: Toll Cascade-regulating Serpinsmentioning

confidence: 80%

“…Purification of Toll Cascade-related Proteins-The native and recombinant forms of the PGRP-SA, GNBP1, GNBP3, MSP, SAE, SPE, and pro-Spätzle proteins were obtained as described previously (10,11).…”

Section: Methodsmentioning

confidence: 99%

“…B, when six Toll cascade-regulating components (each 100 ng) and pro-Spätzle were incubated with Lys-type PG for 5 min as in A, processed Spätzle (12 kDa) was observed by Western blotting with an affinity-purified anti-Spätzle antibody (lane 2). When serpin was added to the reaction mixture, pro-Spätzle process- of the SPs to amplify the pathogen recognition signals (10,11,26). We assumed that endogenous upstream serpin(s) present in small amounts in unstimulated conditions could also be induced as a negative feedback inhibitor in vivo coincident with Toll cascade activation.…”

Section: Three Recombinant Serpins Prevented Pro-spe Activation Leadmentioning

confidence: 99%

“…SPE has been identified as a terminal SP that cleaves pro-Spätzle. Additionally, we provided biochemical evidence of the mechanism by which the GNBP3-mediated ␤-1,3-glucan recognition signal is transferred to pro-Spätzle, leading to the production of AMPs (11). Furthermore, the terminally activated SPE was also shown to convert the 79-kDa Tenebrio pro-PO into PO to generate a melanin complex with SP homolog 1 that is necessary for the production of melanin pigment on the bacterial cell surface, leading to a strong bactericidal effect (7).…”

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confidence: 99%

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Three Pairs of Protease-Serpin Complexes Cooperatively Regulate the Insect Innate Immune Responses

Jiang

Kim

Gong

et al. 2009

Journal of Biological Chemistry

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Serpins are known to be necessary for the regulation of several serine protease cascades. However, the mechanisms of how serpins regulate the innate immune responses of invertebrates are not well understood due to the uncertainty of the identity of the serine proteases targeted by the serpins. We recently reported the molecular activation mechanisms of three serine protease-mediated Toll and melanin synthesis cascades in a large beetle, Tenebrio molitor. Here, we purified three novel serpins (SPN40, SPN55, and SPN48) from the hemolymph of T. molitor. These serpins made specific serpin-serine protease pairs with three Toll cascade-activating serine proteases, such as modular serine protease, Spätzle-processing enzyme-activating enzyme, and Spätzle-processing enzyme and cooperatively blocked the Toll signaling cascade and ␤-1,3-glucanmediated melanin biosynthesis. Also, the levels of SPN40 and SPN55 were dramatically increased in vivo by the injection of a Toll ligand, processed Spätzle, into Tenebrio larvae. This increase in SPN40 and SPN55 levels indicates that these serpins function as inducible negative feedback inhibitors. Unexpectedly, SPN55 and SPN48 were cleaved at Tyr and Glu residues in reactive center loops, respectively, despite being targeted by trypsin-like Spätzle-processing enzyme-activating enzyme and Spätzle-processing enzyme. These cleavage patterns are also highly similar to those of unusual mammalian serpins involved in blood coagulation and blood pressure regulation, and they may contribute to highly specific and timely inactivation of detrimental serine proteases during innate immune responses. Taken together, these results demonstrate the specific regulatory evidences of innate immune responses by three novel serpins.

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Identification of three prophenoloxidase‐activating factors (PPAFs) from an invasive beetle Octodonta nipae Maulik (Coleoptera: Chrysomelidae) and their roles in the prophenoloxidase activation

Zhang

Tang

Lin

et al. 2017

Arch Insect Biochem Physiol

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A typical characteristic of the insect innate immune system is the activation of the serine protease cascade in the hemolymph. As being the terminal component of the extracellular serine protease cascade in the prophenoloxidase (proPO) activating system, proPO-activating factors (PPAFs) activated by the upstream cascade may generate active phenoloxidase, which then induces downstream melanization. In the present study, we reported three PPAFs from the nipa palm hispid beetle Octodonta nipae (Maulik) (designated as OnPPAF1, OnPPAF2, OnPPAF3). All three OnPPAFs contained a single clip domain at the amino-terminus followed by a trypsin-like serine protease domain at the carboxyl-terminus, except the Ser in the active sites of OnPPAF2 and OnPPAF3 was substituted with Gly. Transcript expression analysis revealed that all OnPPAFs were highly expressed in hemolymph, whereas OnPPAF2 showed an extremely low mRNA abundance compared with that of OnPPAF1 and OnPPAF3, and that the abundance of all three OnPPAFs was dramatically increased upon bacterial challenge. Knockdown of OnPPAF1 or OnPPAF3 resulted in a reduction of hemolymph phenoloxidase activity and an inhibition of hemolymph melanization, whereas the knockdown of OnPPAF2 did not affect the proPO cascade. Our work thus implies that the three OnPPAFs may have different functions and regulation during immune responses in O. nipae.

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Proteolytic Cascade for the Activation of the Insect Toll Pathway Induced by the Fungal Cell Wall Component

Cited by 143 publications

References 35 publications

Antimicrobial defence and persistent infection in insects revisited

Antimicrobial defence and persistent infection in insects revisited

Three Pairs of Protease-Serpin Complexes Cooperatively Regulate the Insect Innate Immune Responses

Identification of three prophenoloxidase‐activating factors (PPAFs) from an invasive beetle Octodonta nipae Maulik (Coleoptera: Chrysomelidae) and their roles in the prophenoloxidase activation

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