Nutritional regulation of vitellogenesis in mosquitoes: Implications for anautogeny

Department of Entomology and Institute for Integrative Genome Biology, University of California, Riverside, CA 92521, USA.
Insect Biochemistry and Molecular Biology (Impact Factor: 3.45). 08/2005; 35(7):661-75. DOI: 10.1016/j.ibmb.2005.02.013
Source: PubMed


Anautogeny is a successful reproductive strategy utilized by many mosquito species and other disease-transmitting arthropod vectors. Developing an understanding of the mechanisms underlying anautogeny in mosquitoes is very important because this reproductive strategy is the driving force behind the transmission of disease to millions of people. Information gained from mosquito studies may also be applicable to other blood feeding insect vectors. The conversion of protein from blood into yolk protein precursors for the developing oocytes is an essential part of the reproductive cycle, and understanding how this process is regulated could lead to safe, specific, and effective ways to block reproduction in blood feeding insects. Great gains have been made in elucidating the mechanisms that regulate vitellogenesis in mosquitoes, especially Ae. aegypti. However, a number of questions remain to be answered to make the picture more complete. In this review, we summarize what is currently known about the nutritional regulation of vitellogenesis in mosquitoes and the questions that remain to be answered about this important biological phenomenon.

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Available from: Geoffrey M Attardo, Apr 05, 2014
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    • "Consumption of blood initiate vitellogenesis in the female mosquito during which the fat body produces yolk protein precursors that are absorbed by the developing oocytes [32,33]. Peng et al. [27] exploited this physiology to develop a “vertical DNA vector delivery method” to transiently manipulate gene expression in F0 offspring of plasmid-injected female mosquitoes. "
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    ABSTRACT: Background Susceptibility to Plasmodium infection in Anopheles gambiae has been proposed to result from naturally occurring polymorphisms that alter the strength of endogenous innate defenses. Despite the fact that some of these mutations are known to introduce non-synonymous substitutions in coding sequences, these mutations have largely been used to rationalize knockdown of associated target proteins to query the effects on parasite development in the mosquito host. Here, we assay the effects of engineered mutations on an immune signaling protein target that is known to control parasite sporogonic development. By this proof-of-principle work, we have established that naturally occurring mutations can be queried for their effects on mosquito protein function and on parasite development and that this important signaling pathway can be genetically manipulated to enhance mosquito resistance. Methods We introduced SNPs into the A. gambiae MAPK kinase MEK to alter key residues in the N-terminal docking site (D-site), thus interfering with its ability to interact with the downstream kinase target ERK. ERK phosphorylation levels in vitro and in vivo were evaluated to confirm the effects of MEK D-site mutations. In addition, overexpression of various MEK D-site alleles was used to assess P. berghei infection in A. gambiae. Results The MEK D-site contains conserved lysine residues predicted to mediate protein-protein interaction with ERK. As anticipated, each of the D-site mutations (K3M, K6M) suppressed ERK phosphorylation and this inhibition was significant when both mutations were present. Tissue-targeted overexpression of alleles encoding MEK D-site polymorphisms resulted in reduced ERK phosphorylation in the midgut of A. gambiae. Furthermore, as expected, inhibition of MEK-ERK signaling due to D-site mutations resulted in reduction in P. berghei development relative to infection in the presence of overexpressed catalytically active MEK. Conclusion MEK-ERK signaling in A. gambiae, as in model organisms and humans, depends on the integrity of conserved key residues within the MEK D-site. Disruption of signal transmission via engineered SNPs provides a purposeful proof-of-principle model for the study of naturally occurring mutations that may be associated with mosquito resistance to parasite infection as well as an alternative genetic basis for manipulation of this important immune signaling pathway.
    Parasites & Vectors 06/2014; 7(1):287. DOI:10.1186/1756-3305-7-287 · 3.43 Impact Factor
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    • "Like many but not all hematophagous vectors, female Culicoides sonorensis are anautogenous, requiring a blood meal in order to successfully provision nutrients to the developing oocytes and produce eggs (vitellogenesis). The processes underlying vitellogenesis have been well described in mosquitoes, and result in stimulation of the fat body to induce production of yolk protein precursors (YPPs) that will be transported to the ovary for incorporation in oocytes [43], [44]. YPPs include vitellogenin (Vg), a precursor of the yolk storage protein vitellin, lipophorin (Lp), a lipid transporting lipoprotein, vitellogenic carboxypeptidase (VCP) and vitellogenic cathepsin B (VCB). "
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    ABSTRACT: Unlike other important vectors such as mosquitoes and sandflies, genetic and genomic tools for Culicoides biting midges are lacking, despite the fact that they vector a large number of arboviruses and other pathogens impacting humans and domestic animals world-wide. In North America, female Culicoides sonorensis midges are important vectors of bluetongue virus (BTV) and epizootic hemorrhagic disease virus (EHDV), orbiviruses that cause significant disease in livestock and wildlife. Libraries of tissue-specific transcripts expressed in response to feeding and oral orbivirus challenge in C. sonorensis have previously been reported, but extensive genome-wide expression profiling in the midge has not. Here, we successfully used deep sequencing technologies to construct the first adult female C. sonorensis reference transcriptome, and utilized genome-wide expression profiling to elucidate the genetic response to blood and sucrose feeding over time. The adult female midge unigene consists of 19,041 genes, of which less than 7% are differentially expressed during the course of a sucrose meal, while up to 52% of the genes respond significantly in blood-fed midges, indicating hematophagy induces complex physiological processes. Many genes that were differentially expressed during blood feeding were associated with digestion (e.g. proteases, lipases), hematophagy (e.g., salivary proteins), and vitellogenesis, revealing many major metabolic and biological factors underlying these critical processes. Additionally, key genes in the vitellogenesis pathway were identified, which provides the first glimpse into the molecular basis of anautogeny for C. sonorensis. This is the first extensive transcriptome for this genus, which will serve as a framework for future expression studies, RNAi, and provide a rich dataset contributing to the ultimate goal of informing a reference genome assembly and annotation. Moreover, this study will serve as a foundation for subsequent studies of genome-wide expression analyses during early orbivirus infection and dissecting the molecular mechanisms behind vector competence in midges.
    PLoS ONE 05/2014; 9(5):e98123. DOI:10.1371/journal.pone.0098123 · 3.23 Impact Factor
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    • "ng its nuclear receptor ( ecdysone receptor bound with ultraspiracle protein [ EcR / Usp ] ) , which activates transcription of a series of early genes ( E75 , E74 and Broad ) . These early gene products and 20E bound to EcR / Usp regulate a series of target late genes , which include vitellogenin and other yolk proteins ( Raikhel et al . , 2002 ; Attardo et al . , 2005 ) . Treatment of newly emerged fat bodies from An . gambiae with 20E and the transcriptional inhibitor ACD blocks AgVg splicing ( Fig . 2D ) ; therefore , the effect of 20E requires either new transcription of AgVg and / or early gene transcription . Early gene expression in response to 20E is not dependent on JH exposure ( Zhu et al . "
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    ABSTRACT: Vitellogenesis is one of the most well-studied physiological processes in mosquitoes. Expression of mosquito vitellogenin genes is classically described as being restricted to female adult reproduction. We report premature vitellogenin transcript expression in three vector mosquitoes: Culex tarsalis, Aedes aegypti and Anopheles gambiae. Vitellogenins expressed during non-reproductive stages are alternatively spliced to retain their first intron and encode premature termination codons. We show that intron retention results in transcript degradation by translation-dependent nonsense-mediated mRNA decay. This is probably an example of regulated unproductive splicing and translation (RUST), a mechanism known to regulate gene expression in numerous organisms but which has never been described in mosquitoes. We demonstrate that the hormone 20-hydroxyecdysone (20E) is responsible for regulating post-transcriptional splicing of vitellogenin. After exposure of previtellogenic fat bodies to 20E, vitellogenin expression switches from a non-productive intron-retaining transcript to a spliced protein-coding transcript. This effect is independent of factors classically known to influence transcription, such as juvenile hormone-mediated competence and amino acid signalling through the target of rapamycin pathway. Non-canonical regulation of vitellogenesis through RUST is a novel role for the multifunctional hormone 20E, and may have important implications for general patterns of gene regulation in mosquitoes.
    Insect Molecular Biology 05/2014; 23(4). DOI:10.1111/imb.12092 · 2.59 Impact Factor
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