TRPA5 encodes a thermosensitive ankyrin ion channel receptor in a triatomine insect

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  1. Thanks for your comment - The observation is correct, the current amplitudes are smaller for TRP5A2, compare to TRPV1 and Dmel1, however, there is no possible interpretation of its role in the thermosensation due to this observation. Insect receptor density in heterologous expression systems like HEK cells not necesarily correlates to expression of the gene of interest in native cells. In many cases, a codon optimization is needed to have a detectable expression (doi: 10.3389/fncel.2021.744401), showing that the expression in HEK cells does not recapitulate native expression patterns

  2. This is a beautiful and very detailed paper using multiple approaches to carefully dissect the role of an unknown channel. The thermosensitivity of the TRPA5 channel is clear and compelling, and although its role in noxious heat sensing is not yet validated, it is a strong hypothesis. Overall the use of multiple lines of evidence, and particularly matching evolutionary biology, structural modelling, and cellular physiology is extremely impressive and a strong addition to the field.

  3. rapidly reach temperatures above 60°C if exposed to full sun, suggesting that TRPA5 may mediate noxious heat avoidance

    How interesting! Is this unique to Rhodnius or true of all species that express TRPA52?

  4. emarkably similar to the expression pattern of Pyrexia in the fruit fly

    This paper seems to show preferential nervous system expression of Pyrexia, is that true of TRPA52?

  5. Notably, a known noxious heat receptor in Diptera, Pyrexia, is missing from Rhodnius, while a TRPA5 ortholog has not been found in flies and mosquitoes, raising the interesting possibility that convergence and functional redundancy might account for the evolutionary patterns of differential gain and retention of thermoTRPs in insects.

    Based on the unique thermal sensitivity of TRP5A2 relative to Pyrexia and the other thermosensitive channels, in what ways is it redundant/convergent and in what ways is it innovative? Behaviorally, does Rhodnius have higher thresholds for noxious heat responses?

  6. whole cell currents were evoked by temperature steps from 53°C to 68°C (Fig. 3D, 3E)

    The temperature-evoked current changes with TRPA52 seems substantially smaller than the other profiled thermosensitive channels. Could you directly compare the current changes between these channels? How does the reduced current (if that is accurate) from TRPA52 change its role?

  7. First, we used the ionic current increments through the open patch pipette (holding potential −2 mV), to calculate the temperature changes associated with the different laser intensities.

    I got a little confused here by the role of the open patch pipette and the calibration that was used, and how it related to the expression of the ion channels referenced in the previous sentence. It seemed to me at first the calibration was somehow specific to the transient expression of the known thermoTRPs (which was clarified by reading the great methods section!). Referencing the methods and a little more information on the calibration in the text could help.

  8. TRPA52 is significantly enriched in adult male and female heads (Fig. 1B, Fig. S3, Table S5). We further examined expression profiles of Rp-TRPA52 via quantitative PCR of additional canonical sensory tissues. Rp-TRPA52 is abundant in the rostrum and legs and expressed at lower levels in antennae (Fig. 1B, Fig. S3), a first indication in line with a possible role in thermosensation.

    This expression pattern is interesting, but it's not immediately obvious to me how the magnitude of tissue expression relates to heat sensing. For example, is it known that Rhodnius preferentially sense heat with their head far more than their antennae? Profiling TRPA52 expression in tissues unrelated to sensation, showing specific localization or enrichment to sensory neurons, or linking the highly expressed tissues with known behavior might all help clarify how this suggestive tissue expression pattern is linked to heat sensing!