Two insulin-like peptide family members from the mosquito Aedes aegypti exhibit differential biological and receptor binding activities

Wen, Zheng; Gulia, Monika; Clark, Kevin D.; Dhara, Animesh; Crim, Joe W.; Strand, Michael R.; Brown, Mark R.

doi:10.1016/j.mce.2010.07.003

Cited by 76 publications

(102 citation statements)

References 51 publications

(102 reference statements)

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“…This type of signaling regulation may also occur in insects. Wen et al (Wen et al, 2010) showed that A. aegypti ILP3 bound to MIR in isolated ovary membranes with much higher affinity than did ILP4 or bovine insulin, indicating that the MIR varies in its affinity for endogenous ILPs as well as for mammalian insulin. Similarly, the Drosophila melanogaster insulin receptor can respond to different ILP ligands, as shown by the ability of DILP5 isoforms and IGFs to competitively displace human insulin from the fruit fly insulin receptor (Sajid et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

Human IGF1 extends lifespan and enhances resistance to Plasmodium falciparum infection in the malaria vector Anopheles stephensi

Drexler

Nuss

Hauck

et al. 2013

Journal of Experimental Biology

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SUMMARYThe highly conserved insulin/insulin-like growth factor (IGF) signaling (IIS) pathway regulates metabolism, development, lifespan and immunity across a wide range of organisms. Previous studies have shown that human insulin ingested in the blood meal can activate mosquito IIS, resulting in attenuated lifespan and increased malaria parasite infection. Because human IGF1 is present at higher concentrations in blood than insulin and is functionally linked with lifespan and immune processes, we predicted that human IGF1 ingested in a blood meal would affect lifespan and malaria parasite infection in the mosquito Anopheles stephensi. Here we demonstrate that physiological levels of ingested IGF1, like insulin, can persist intact in the blood-filled midgut for up to 30h and disseminate into the mosquito body, and that both peptides activate IIS in mosquito cells and midgut. At these same levels, ingested IGF1 alone extended average mosquito lifespan by 23% compared with controls and, more significantly, when ingested in infected blood meals, reduced the prevalence of Plasmodium falciparum-infected mosquitoes by >20% and parasite load by 35-50% compared with controls. Thus, the effects of ingested IGF1 on mosquito lifespan and immunity are opposite to those of ingested insulin. These results offer the first evidence that insect cells can functionally discriminate between mammalian insulin and IGF1. Further, in light of previous success in genetically targeting IIS to alter mosquito lifespan and malaria parasite transmission, this study indicates that a more complete understanding of the IIS-activating ligands in blood can be used to optimize transgenic strategies for malaria control.

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Section: Discussionmentioning

confidence: 99%

Human IGF1 extends lifespan and enhances resistance to Plasmodium falciparum infection in the malaria vector Anopheles stephensi

Drexler

Nuss

Hauck

et al. 2013

Journal of Experimental Biology

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“…Aedes aegypti ILP3 (AaILP3) and ILP4 (AaILP4) were synthesized as previously described (Brown et al, 2008;Wen et al, 2010). 20E (Sigma) was solubilized in absolute ethanol.…”

Section: Reagentsmentioning

confidence: 99%

“…10902, Gibco, Gaithersburg, MD, USA) alone or with other reagents. ECD content in each sample of medium (50l) was determined by radioimmunoassay (RIA) (Wen et al, 2010). Total protein was determined for abdomen walls (i.e.…”

Section: First Clutch In Vivo Assaysmentioning

confidence: 99%

“…Oogenesis remains arrested, however, until a blood meal is taken, which triggers the release of insulin-like peptides (ILPs) and ovary ecdysteroidogenic hormone (OEH) from neurosecretory cells in the brain (Riehle et al, 2006;Brown et al, 1998). ILP3, ILP4 and OEH stimulate the ovaries to produce ECD (Brown et al, 1998;Brown et al, 2008;Wen et al, 2010). ILP3 together with amino acid sensing through the TOR pathway induces serine protease activity in the midgut that digests the blood meal, while ILP3, TOR and ECD interact to upregulate the expression of vitellogenin (VG) and other yolk proteins by the fat body Roy et al, 2007;Bryant et al, 2010;Roy and Raikhel, 2011;Gulia-Nuss et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

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Ovary ecdysteroidogenic hormone activates egg maturation in the mosquito, Georgecraigius atropalpus, after adult eclosion or a blood meal

Gulia-Nuss

Eum

Strand

et al. 2012

Journal of Experimental Biology

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SUMMARYThe rockpool mosquito, Georgecraigius atropalpus, is a facultatively autogenous species that produces its first egg clutch without a blood meal shortly after emergence. Several days after depositing this clutch, females must take a blood meal to produce a second egg clutch. Decapitation of females shortly after emergence or blood ingestion prevents egg maturation. Here, we report that a single injected dose of the neuropeptide ovary ecdysteroidogenic hormone (OEH) fully restored egg maturation in decapitated females in both circumstances. This neuropeptide and two insulin-like peptides (ILPs) are potent gonadotropins in the related yellow fever mosquito, Aedes aegypti. ILP3 was marginally restorative in decapitated G. atropalpus, and ILP4 had no effect. Egg maturation in non-and blood-fed G. atropalpus was dependent on the enzymatic mobilization of amino acids from stored protein or the blood meal for yolk protein (vitellogenin, VG) synthesis and uptake by oocytes. We further show that OEH stimulates serine protease activity in the fat body of newly eclosed females or in the midgut of blood-fed ones, and ecdysteroid hormone production by the ovaries of both females. In contrast, only 20-hydroxyecdysone stimulated VG synthesis in the fat body of non-and blood-fed females. Using RNA interference to knock down expression of the insulin receptor, we found that OEH still fully restored autogenous egg maturation. In summary, our results identify OEH as a primary regulator of egg maturation in both autogenous and blood-fed G. atropalpus females and suggest the shift from blood meal-dependent to blood meal-independent release of OEH is a key factor in the evolution of autogeny in this species.

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“…Studies in A. aegypti also establish that ILP3 activity depends upon binding to the insulin receptor (IR), a receptor tyrosine kinase (RTK), which triggers phosphorylation of downstream components in the insulin signaling pathway including Akt (4,9,14). OEH in contrast belongs to a poorly characterized family of neuropeptides known only from arthropods called neuroparsins (13,15,16).…”

mentioning

confidence: 99%

Ovary ecdysteroidogenic hormone requires a receptor tyrosine kinase to activate egg formation in the mosquito Aedes aegypti

Vogel

Brown

Strand

2015

Proc. Natl. Acad. Sci. U.S.A.

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121

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Mosquitoes are major disease vectors because most species must feed on blood from a vertebrate host to produce eggs. Blood feeding by the vector mosquito Aedes aegypti triggers the release of two neurohormones, ovary ecdysteroidogenic hormone (OEH) and insulin-like peptides (ILPs), which activate multiple processes required for egg formation. ILPs function by binding to the insulin receptor, which activates downstream components in the canonical insulin signaling pathway. OEH in contrast belongs to a neuropeptide family called neuroparsins, whose receptor is unknown. Here we demonstrate that a previously orphanized receptor tyrosine kinase (RTK) from A. aegypti encoded by the gene AAEL001915 is an OEH receptor. Phylogenetic studies indicated that the protein encoded by this gene, designated AAEL001915, belongs to a clade of RTKs related to the insulin receptor, which are distinguished by an extracellular Venus flytrap module. Knockdown of AAEL001915 by RNAi disabled OEH-mediated egg formation in A. aegypti. AAEL001915 was primarily detected in the mosquito ovary in association with follicular epithelial cells. Both monomeric and dimeric AAEL001915 were detected in mosquito ovaries and transfected Drosophila S2 cells. Functional assays further indicated that OEH bound to dimeric AAEL001915, which resulted in downstream phosphorylation of Ak strain transforming factor (Akt). We hypothesize that orthologs of AAEL001915 in other insects are neuroparsin receptors.insect | vector | reproduction | mosquito | oogenesis

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Two insulin-like peptide family members from the mosquito Aedes aegypti exhibit differential biological and receptor binding activities

Cited by 76 publications

References 51 publications

Human IGF1 extends lifespan and enhances resistance to Plasmodium falciparum infection in the malaria vector Anopheles stephensi

Human IGF1 extends lifespan and enhances resistance to Plasmodium falciparum infection in the malaria vector Anopheles stephensi

Ovary ecdysteroidogenic hormone activates egg maturation in the mosquito, Georgecraigius atropalpus, after adult eclosion or a blood meal

Ovary ecdysteroidogenic hormone requires a receptor tyrosine kinase to activate egg formation in the mosquito Aedes aegypti

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