Identification and functional characterization of a novel locust peptide belonging to the family of insect growth blocking peptides

Duressa, Tewodros Firdissa; Boonen, Kurt; Hayakawa, Yoichi; Huybrechts, Roger

doi:10.1016/j.peptides.2015.09.011

Cited by 8 publications

(11 citation statements)

References 43 publications

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“…Locusta migratoria GBP was reported by Durressa et al. (Duressa et al., 2015). Other peptide sequences are in the prior report (Matsumoto et al., 2012).…”

Section: Nonlepidopteran Gbpmentioning

confidence: 78%

“…Comparisons of these peptides enabled us to extract the consensus motif C-x(2)-G-x(4,6)-G-x(1,2)-C-[KR] (Matsumoto et al., 2012). More recently, this motif has been found in Locusta migratoria and Schistocerca gregaria GBPs (Duressa et al., 2015). Here, we describe the phylogenetic relationship derived from precursor protein sequences of all known members of the GBP family and GBP orthologs which were identified by homology searches (Figure 1).…”

Section: Nonlepidopteran Gbpmentioning

confidence: 84%

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Functional Multiplicity of an Insect Cytokine Family Assists Defense Against Environmental Stress

Shears

Hayakawa

2019

Front. Physiol.

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The widespread distribution of insects over many ecological niches owes much to evolution of multiple mechanisms to defend against environmental stress, especially because their ectothermic nature and small body size render them particularly susceptible to extremes in temperature and water availability. In this review, we will summarize the latest information describing a single, multifunctional cytokine family that is deployed by six orders of insect species to combat a diverse variety of environmental stresses. The originating member of this peptide family was identified in Mythimna (formerly called Pseudaletia ) separata armyworm; the cytokine was named growth-blocking peptide (GBP), reflecting its actions in combating parasitic invasion. The peptide’s name has been retained, though the list of its regulatory activities has greatly expanded. All members of this family are small peptides, 19–25 amino acid residues, whose major source is fat body. They are now known to regulate embryonic morphogenesis, larval growth rates, feeding activities, immune responses, nutrition, and aging. In this review, we will describe recent developments in our understanding of the mechanisms of action of the GBP family, but we will also highlight remaining gaps in our knowledge.

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“…Locusta migratoria GBP was reported by Durressa et al. (Duressa et al., 2015). Other peptide sequences are in the prior report (Matsumoto et al., 2012).…”

Section: Nonlepidopteran Gbpmentioning

confidence: 78%

Section: Nonlepidopteran Gbpmentioning

confidence: 84%

Functional Multiplicity of an Insect Cytokine Family Assists Defense Against Environmental Stress

Shears

Hayakawa

2019

Front. Physiol.

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“…In contrast to vertebrates, only few cytokines or cytokine-like peptides have been identified in insects (Duressa et al, 2015; Schrag et al, 2017; Matsumura et al, 2018). Expression of CRLF3 by locust hemocytes and brain cells may indicate multiple production sites of its endogenous ligand, since blood-brain-barriers restrict the exchange of ions and soluble molecules (reviewed in DeSalvo et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

“…Potential production sites, that release the ligand into the circulation, are certain types of hemocytes, neurosecretory organs including the corpora allata as well as the corpora cardiaca, and the fat body. They contain and release also other cytokines involved in stress responses (Duressa et al, 2015; Matsumura et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

The Orphan Cytokine Receptor CRLF3 Emerged With the Origin of the Nervous System and Is a Neuroprotective Erythropoietin Receptor in Locusts

Hahn

Büschgens

Schwedhelm-Domeyer

et al. 2019

Front. Mol. Neurosci.

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The orphan cytokine receptor-like factor 3 (CRLF3) was identified as a neuroprotective erythropoietin receptor in locust neurons and emerged with the evolution of the eumetazoan nervous system. Human CRLF3 belongs to class I helical cytokine receptors that mediate pleiotropic cellular reactions to injury and diverse physiological challenges. It is expressed in various tissues including the central nervous system but its ligand remains unidentified. A CRLF3 ortholog in the holometabolous beetle Tribolium castaneum was recently shown to induce anti-apoptotic mechanisms upon stimulation with human recombinant erythropoietin. To test the hypothesis that CRLF3 represents an ancient cell-protective receptor for erythropoietin-like cytokines, we investigated its presence across metazoan species. Furthermore, we examined CRLF3 expression and function in the hemimetabolous insect Locusta migratoria. Phylogenetic analysis of CRLF3 sequences indicated that CRLF3 is absent in Porifera, Placozoa and Ctenophora, all lacking the traditional nervous system. However, it is present in all major eumetazoan groups ranging from cnidarians over protostomians to mammals. The CRLF3 sequence is highly conserved and abundant amongst vertebrates. In contrast, relatively few invertebrates express CRLF3 and these sequences show greater variability, suggesting frequent loss due to low functional importance. In L. migratoria, we identified the transcript Lm-crlf3 by RACE-PCR and detected its expression in locust brain, skeletal muscle and hemocytes. These findings correspond to the ubiquitous expression of crlf3 in mammalian tissues. We demonstrate that the sole addition of double-stranded RNA to the culture medium (called soaking RNA interference) specifically interferes with protein expression in locust primary brain cell cultures. This technique was used to knock down Lm-crlf3 expression and to abolish its physiological function. We confirmed that recombinant human erythropoietin rescues locust brain neurons from hypoxia-induced apoptosis and showed that this neuroprotective effect is absent after knocking down Lm-crlf3. Our results affirm the erythropoietin-induced neuroprotective function of CRLF3 in a second insect species from a different taxonomic group. They suggest that the phylogenetically conserved CRLF3 receptor may function as a cell protective receptor for erythropoietin or a structurally related cytokine also in other animals including vertebrate and mammalian species.

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“…Several hemolymph proteins directly interfere with invading pathogens (anti-microbial peptides; reviewed by Yi et al, 2014;Wu et al, 2018) or activate hemocytes to neutralize pathogens by various mechanisms (plasmatocyte spreading peptides, growth blocking peptides, and paralytic peptides; Strand, 2008;Duressa et al, 2015). Other hemolymph proteins initiate physiological adaptations of insect tissues, supporting cell survival and functionality in challenging conditions.…”

Section: Introductionmentioning

confidence: 99%

Locust Hemolymph Conveys Erythropoietin-Like Cytoprotection via Activation of the Cytokine Receptor CRLF3

et al. 2021

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The cytokine receptor-like factor 3 (CRLF3) is an evolutionary conserved class 1 cytokine receptor present in all major eumetazoan groups. Endogenous CRLF3 ligands have not been identified and the physiological responses mediated by mammalian CRLF3 are poorly characterized. Insect CRLF3 is activated by erythropoietin (Epo) and several related molecules that protect mammalian neurons from stress-induced apoptosis. However, insects neither express Epo nor “classical” Epo receptor. Cell-protective effects of insect hemolymph have been described for several species. In this study, we explored the possibility that the endogenous CRLF3 ligand is contained in locust hemolymph. PCR analyses confirmed expression of crfl3-transcripts in neurons and hemocytes of Locusta migratoria and Tribolium castaneum. Survival of locust hemocytes in primary cultures was significantly increased by supplementation of culture medium with locust hemolymph serum. Locust primary neuron cultures were also protected by locust hemolymph, though preceding exposure to fetal bovine serum changed the hemolymph dose-dependency of neuroprotection. Direct comparison of 10% hemolymph serum with recombinant human Epo in its optimal neuroprotective concentration revealed equivalent anti-apoptotic effects on hypoxia-exposed locust neurons. The same concentration of locust hemolymph serum also protected hypoxia-exposed T. castaneum neurons. This indicates that the neuroprotective factor in locust hemolymph is sufficiently conserved in insects to allow activation of neuroprotective receptors in different species. Locust hemolymph-induced neuroprotection in both L. migratoria and T. castaneum was abolished after RNAi-mediated suppression of crlf3-expression. In summary, we report the presence of a conserved endogenous cytokine in locust hemolymph that activates CRLF3 and connected anti-apoptotic processes in hemocytes and neurons. Identification and characterization of the CRLF3 ligand will promote knowledge about cytokine evolution and may unravel cell-protective agents with potential clinical application.

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Identification and functional characterization of a novel locust peptide belonging to the family of insect growth blocking peptides

Cited by 8 publications

References 43 publications

Functional Multiplicity of an Insect Cytokine Family Assists Defense Against Environmental Stress

Functional Multiplicity of an Insect Cytokine Family Assists Defense Against Environmental Stress

The Orphan Cytokine Receptor CRLF3 Emerged With the Origin of the Nervous System and Is a Neuroprotective Erythropoietin Receptor in Locusts

Locust Hemolymph Conveys Erythropoietin-Like Cytoprotection via Activation of the Cytokine Receptor CRLF3

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