The ion channel ppk301 controls freshwater egg-laying in the mosquito Aedes aegypti
Abstract
Female Aedes aegypti mosquitoes are deadly vectors of arboviral pathogens and breed in containers of freshwater associated with human habitation. Because high salinity is lethal to offspring, correctly evaluating water purity is a crucial parenting decision. We found that the DEG/ENaC channel ppk301 and sensory neurons expressing ppk301 control egg-laying initiation and choice in Ae. aegypti. Using calcium imaging, we found that ppk301-expressing cells show ppk301-dependent responses to water but, unexpectedly, also respond to salt in a ppk301-independent fashion. This suggests that ppk301 is instructive for egg-laying at low salt concentrations, but that a ppk301-independent pathway is responsible for inhibiting egg-laying at high salt concentrations. Water is a key resource for insect survival and understanding how mosquitoes interact with water to control different behaviors is an opportunity to study the evolution of chemosensory systems.
Data availability
Source data for all plots in Figures 1-3 and Figure 5-7 are provided in Supplementary File 1.
-
The neurotranscriptome of the Aedes aegypti mosquito.NCBI BioProject, PRJNA236239.
-
| Improved reference genome of Aedes aegypti informs arbovirus vector control.NCBI Assembly, GCF_002204515.2.
Article and author information
Author details
Funding
Howard Hughes Medical Institute
- Benjamin J Matthews
- Leslie B Vosshall
Jane Coffin Childs Memorial Fund for Medical Research
- Benjamin J Matthews
- Meg A Younger
Grass Foundation
- Meg A Younger
Leon Levy Foundation
- Meg A Younger
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: For routine strain maintenance, animals were blood-fed on live mice or human subjects. Adult females of all genotypes were blood-fed on a single human subject during mutant generation, for behavioral assays, and calcium imaging. Blood-feeding procedures with live hosts were approved and monitored by The Rockefeller University Institutional Animal Care and Use Committee (IACUC protocol 15772) and Institutional Review Board, (IRB protocol LV-0652). Human subjects gave their written informed consent to participate.
Human subjects: For routine strain maintenance, animals were blood-fed on live mice or human subjects. Adult females of all genotypes were blood-fed on a single human subject during mutant generation, for behavioral assays, and calcium imaging. Blood-feeding procedures with live hosts were approved and monitored by The Rockefeller University Institutional Animal Care and Use Committee (IACUC protocol 15772) and Institutional Review Board, (IRB protocol LV-0652). Human subjects gave their written informed consent to participate.
Copyright
© 2019, Matthews et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 7,313
- views
-
- 905
- downloads
-
- 86
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Further reading
-
- Genetics and Genomics
Resistance to anthelmintics, particularly the macrocyclic lactone ivermectin (IVM), presents a substantial global challenge for parasite control. We found that the functional loss of an evolutionarily conserved E3 ubiquitin ligase, UBR-1, leads to IVM resistance in Caenorhabditis elegans. Multiple IVM-inhibiting activities, including viability, body size, pharyngeal pumping, and locomotion, were significantly ameliorated in various ubr-1 mutants. Interestingly, exogenous application of glutamate induces IVM resistance in wild-type animals. The sensitivity of all IVM-affected phenotypes of ubr-1 is restored by eliminating proteins associated with glutamate metabolism or signaling: GOT-1, a transaminase that converts aspartate to glutamate, and EAT-4, a vesicular glutamate transporter. We demonstrated that IVM-targeted GluCls (glutamate-gated chloride channels) are downregulated and that the IVM-mediated inhibition of serotonin-activated pharynx Ca2+ activity is diminished in ubr-1. Additionally, enhancing glutamate uptake in ubr-1 mutants through ceftriaxone completely restored their IVM sensitivity. Therefore, UBR-1 deficiency-mediated aberrant glutamate signaling leads to ivermectin resistance in C. elegans.
-
- Genetics and Genomics
Osteoporosis, characterized by reduced bone density and strength, increases fracture risk, pain, and limits mobility. Established therapies of parathyroid hormone (PTH) analogs effectively promote bone formation and reduce fractures in severe osteoporosis, but their use is limited by potential adverse effects. In the pursuit of safer osteoporosis treatments, we investigated R25CPTH, a PTH variant wherein the native arginine at position 25 is substituted by cysteine. These studies were prompted by our finding of high bone mineral density in a hypoparathyroidism patient with the R25C homozygous mutation, and we explored its effects on PTH type-1 receptor (PTH1R) signaling in cells and bone metabolism in mice. Our findings indicate that R25CPTH(1–84) forms dimers both intracellularly and extracellularly, and the synthetic dimeric peptide, R25CPTH(1–34), exhibits altered activity in PTH1R-mediated cyclic AMP (cAMP) response. Upon a single injection in mice, dimeric R25CPTH(1–34) induced acute calcemic and phosphaturic responses comparable to PTH(1–34). Furthermore, repeated daily injections increased calvarial bone thickness in intact mice and improved trabecular and cortical bone parameters in ovariectomized (OVX) mice, akin to PTH(1–34). The overall results reveal a capacity of a dimeric PTH peptide ligand to activate the PTH1R in vitro and in vivo as PTH, suggesting a potential path of therapeutic PTH analog development.