Ganglion-specific splicing of TRPV1 underlies infrared sensation in vampire bats

Abstract

Vampire bats (Desmodus rotundus) are obligate blood feeders that have evolved specialized systems to suit their unique sanguinary lifestyle 1–3. Chief among such adaptations is the ability to detect infrared radiation as a means of locating hot spots on warm-blooded prey. Among vertebrates, only vampire bats, boas, pythons, and pit vipers are capable of detecting infrared radiation 1,4. In each case, infrared heat is detected by trigeminal nerve fibers that innervate specialized pit organs on the animal’s face 5–10. Thus, vampire bats and snakes have taken thermosensation to the extreme by developing specialized systems for detecting infrared radiation. As such, these creatures provide a window into the molecular and genetic mechanisms underlying evolutionary tuning of thermoreceptors in a species or cell type specific manner. Previously, we have shown that snakes co-opt a non-heat sensitive channel (vertebrate TRPA1) to produce an infrared detector 6. Here we show that vampire bats tune an already heat sensitive channel (TRPV1) by lowering its thermal activation threshold to ~30°C. This is achieved through alternative splicing of TRPV1 transcripts to produce a channel with a truncated C-terminal cytoplasmic domain. Remarkably, these splicing events occur exclusively in trigeminal ganglia (TG), and not dorsal root ganglia (DRG), thereby maintaining a role for TRPV1 as a detector of noxious heat in somatic afferents. This reflects a unique organization of the bat TRPV1 gene that we show to be characteristic of Laurasiatheria mammals (cows, dogs, and moles), supporting a close phylogenetic relationship with bats. These findings reveal a unique molecular mechanism for physiological tuning of thermosensory nerve fibers.

Carboxyl-terminal Domain of Transient Receptor Potential Vanilloid 1 Contains Distinct Segments Differentially Involved in Capsaicin- and Heat-induced Desensitization

“…TRPV1 CTD has been implicated in heat activation (6,28,39). The chimeric approach provided a clue as to the roles of TRPV1 CTD in heat-induced desensitization.…”

“…Both TRPV1 ctV3 and ctV3(B) showed reduced ⌬H°, suggesting that the altered heat sensitivity of ctV3 and ctV3(B) is commonly derived from the alteration of the distal half of CTD. Altered heat sensitivity conferred by truncation of the distal half of the CTD has been reported in rat TRPV1 and in tissue-specific splicing variants of TRPV1 in vampire bats (28,39,40). In contrast to activation, TRPV1 ctV3(B) displayed heat-induced desensitization similar to WT, whereas ctV3 lacked heat-induced desensitization.…”

Low-cost functional plasticity of TRPV1 supports heat tolerance in squirrels and camels

“…For example, chicken TRPV1 has a relatively high (46°C) apparent temperature activation threshold, which can be viewed as an adaptation of the somatosensory system to the high core body temperature of birds (32). In contrast, a TRPV1 isoform from the trigeminal ganglion of vampire bats (apparent activation threshold 30°C) was suggested to serve as a low radiant heat sensor driving the detection of superficial blood vessels in the bat's warm-blooded prey (33). In both cases, Data are normalized to maximal activity evoked by 5 μM capsaicin.…”

“…Our attempts to backengineer heat sensitivity led to the identification of a pair of amino acids (Asn126/Glu190 and Asn124/Glu188 in squirrel and camel, respectively), which, when mutated to Ser and Gln, respectively, are sufficient to restore temperature gating of the channels to the level of the rat ortholog. Sequence analysis of TRPV1 channels from different species shows that the Asn→Ser and Glu→Gln mutations did not restore a prerequisite heat-sensing sequence of TRPV1, because the Asn/Glu pair is also present in a number of TRPV1 orthologs (cow, vampire bat, coastal mole, chicken, zebrafish), which display robust heat sensitivity in the 28-46°C range (Table S2) (32,33). In the crystal structure of the rTRPV1 N-terminal domain, Ser124 is located in the C-terminal part of the inner helix of ankyrin repeat 1, whereas Gln188 is part of the α-helix between the repeats 2 and 3 ( Fig.…”

“…Studies in TRPV1 showed that heat sensitivity can be altered by mutations in virtually any channel domain (33,(40)(41)(42)(43)(44)(45)(46), supporting the idea that molecular determinants of the hypothetical heat-sensing module are not localized in a single topologically defined channel element, but are instead distributed throughout the molecule (35). Although a full-length structure of TRPV1 is currently unavailable, the recent cryo-EM structure of TRPA1 revealed tight interations between the N-and C-termini (47), suggesting that topologically distant domains could be functionally coupled, in which case mutations that affect heat sensing or coupling mechanisms could be functionally indistinguishable.…”