A spatial map of antennal-expressed olfactory ionotropic receptors in the malaria mosquito
Posted on: 2 June 2022 , updated on: 11 May 2023
Preprint posted on 12 May 2022
Would an olfactory receptor in any other place smell just as sweet? Ionotropic receptor position on the mosquito antenna.
Selected by T. W. SchwanitzCategories: bioinformatics, molecular biology, neuroscience
Updated 11 May 2023 with a postLight by T. W. Schwanitz
This study was published in Cell Reports with numerous intriguing updates and revisions. A third author is now on the paper, underscoring just how much got added. The most fascinating updates for me are the functional and behavioral follow-ups. The original preprint relied on in situ probes, so the inclusion of supporting data from a transgenic line for IR41c that almost perfectly matches the conclusions from the in situ probes is very reassuring. The calcium imaging results for these IR41c neurons reveal unexpected inhibitory responses to some odorants.
The authors addressed one initial question by including additional age groups in their study. The different age groups didn’t show any changes in in situ IR gene expression, which means that differences in the number of IRs expressed likely do not result from gross changes in the number of IR neurons. Instead, these changes in expression could be the result of an increase in the number of IR receptors per neuron.
The heatmap in what is now figure 1E has changed: the authors kept the version organized by transcript abundance and altered the color scheme. Overall, the new color scheme is nicer, but it does obscure some of the stand-out IRs a bit, instead putting emphasis on the co-receptors. IR41c, for example, is a bit of an outlier in a few of the studies, but that is not very obvious with the new color scheme. This is an instance where consulting both the preprint and the final paper can assist with data visualization.
Overall, this is a fascinating and detailed study where a lot was added between the preprint and the final publication: numerous additional figures and panels help to portray the results, and substantial textual revisions help the reader to contextualize the findings.
Background: Location, location, location: as with real estate, location matters for olfactory receptors. Mosquito olfactory receptors are mostly located on the antennae (Fig. 1A). But how are olfactory receptors distributed there, and how does that affect their sense of smell? In Drosophila melanogaster, the structures that house olfactory receptors—the sensilla—are localized to specific regions of the antennae (Vosshall and Stocker, 2007). In contrast, mosquito antennae have a more regular distribution of sensilla (Seenivasagan et al., 2009). Nevertheless, when Raji and Potter investigated the spatial distribution of the ionotropic receptors housed within these sensilla, they found that the receptors were not evenly distributed.
To detect airborne molecules, the mosquito olfactory system uses many different types of receptors, such as gustatory receptors, odorant receptors, and ionotropic receptors. The latter are ion channels that have a binding site for specific odorants. Usually, a “tuning ionotropic receptor” is tuned to a certain odorant or class of odorants. It forms a complex with an “ionotropic coreceptor,” an ionotropic receptor that isn’t linked to just one group of compounds. Ionotropic receptors appear to be especially good at detecting acids and amines; hence, they may influence the preference some mosquitoes have for biting human beings, as amines could be one component of human odor that attracts mosquitoes (Chen et al., 2019).
The two species investigated in this preprint are both members of the confusing Anopheles gambiae species complex: An. gambiae s. s. (S form) and An. coluzzii (M form). While the exact taxonomic classification of these mosquitoes is unclear, their effect on humanity is hard to overlook—the malaria parasite that they transmit has been and still is one of the deadliest human pathogens. They make such good vectors because of their predilection for biting human beings and their preference for human odor. Deeper understanding of mosquito ionotropic receptors could facilitate better mosquito control methods.
Fig. 1A. Head of the Anopheles gambiae mosquito, with a schematic to show the antennae and mouthparts.
Key findings:
- Using whole-mount fluorescent in situ hybridization for four tuning ionotropic receptors (IRs 7w, 41c, 41t.2, 75l) and three ionotropic coreceptors (IRs 25a, 76b, and 8a), the authors show that these receptors are not evenly distributed on the antenna. Generally, tuning ionotropic receptors tend to be on the part of the antenna furthest from the head. Even two of the three coreceptors tested (IRs 25a and 76b) were most expressed on the distal half of the antenna (while IR8a seems to be common throughout the antenna; see Fig. 2).
- These results were consistent across multiple individuals, though there are notable differences between males and females, e.g., males do not express IRs on the first ten segments closest to their head and IR41t.2 expression is enriched in male antennae.
- The authors conducted a transcriptome analysis and then used that data to conduct in situ probes of all 20 additional ionotropic receptors that they found upregulated in the transcriptome. Again, they revealed that these receptors tend to be most expressed toward the distal end of the antenna. IR93a makes for a striking example, as 80% of the cells expressing it were on the 13th flagellomere, which is the final antennal segment at the very tip. Testing a limited number of these receptors in males confirmed the trend observed in females.
- Next, Raji and Potter used two probe whole mount in situs to examine co-expression among ionotropic coreceptors and four highly expressed tuning receptors. They found numerous interesting trends, e.g., IRs 7w and 75l overlap with IR8a, a coreceptor that has been previously linked to acid-sensitive tuning ionotropic receptors. This overlap suggests that the two tuning receptors could also be linked to acids. These results show that simply examining patterns of intersection can lead to hypotheses about receptor function.
- The authors also found that the number of ionotropic receptors expressed per flagellomere (antennal segment) seems to be consistent across individuals; however, the exact location of a receptor within a flagellomere is highly variable among individuals.
Fig. 2. Different receptors fluorescing along the mosquito antennae. Next to each full antenna is an inset of the region with the highest expression. Note that in D, IR751 is most expressed toward the proximal part of the antenna while the other receptors shown are most expressed in the distal portion.
Questions for the authors:
- You mention that your study is a “snapshot” of the expression of ionotropic receptors in mosquitoes that are five-to-seven days old. Are there any plans to look at other age ranges? Could there be any interesting insights from looking at ionotropic receptor expression in larvae or pupae? And would your in situ probes be possible in larval antennae?
- There are a lot of tantalizing instances of co-expression in your paper that seem like they could be worth follow-up studies, e.g., IR751 and IR8a being co-expressed suggests that IR751 is likely sensitive to acids. If you could only do functional studies on one of these combinations (empty neuron studies, for example), which combination would you investigate further, and why?
- Any speculation as to why ionotropic receptors are most expressed on the distal portion of the antenna and not the proximal portion?
- Do you think that odorant receptors could share a similar pattern of distribution along the antenna?
Why I think this study is important:
Where is it? What is it? How does it work? These are some of the most fundamental questions that can be asked about something, and they serve as the basis for more complex follow-up questions. By shedding light (and fluorescence) on the location of ionotropic receptors, Raji and Potter lay the groundwork for more precise studies. Knowing that a given receptor is mostly found on the distal part of the antenna means that studies investigating this receptor could focus on collecting only that part of the antennae, thus reducing background noise. Moreover, the authors make use of an interesting method that can reveal new insights about the function of different receptors.
References:
Chen, Z., Liu, F., & Liu, N. (2019). Human odour coding in the yellow fever mosquito, Aedes aegypti. Scientific reports, 9(1), 1-12.
Seenivasagan, T., Sharma, K. R., Shrivastava, A., Parashar, B. D., Pant, S. C., & Prakash, S. (2009). Surface morphology and morphometric analysis of sensilla of Asian tiger mosquito, Aedes albopictus (Skuse): an SEM investigation. Journal of vector borne diseases, 46(2), 125.
Vosshall, L. B., & Stocker, R. F. (2007). Molecular architecture of smell and taste in Drosophila. Annu. Rev. Neurosci., 30, 505-533.
doi: https://doi.org/10.1242/prelights.32219
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