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

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Vampire bats (Desmodus rotundus) are obligate blood feeders that have evolved specialized systems to suit their sanguinary lifestyle1, 2, 3. Chief among such adaptations is the ability to detect infrared radiation as a means of locating hotspots on warm-blooded prey. Among vertebrates, only vampire bats, boas, pythons and pit vipers are capable of detecting infrared radiation1, 4. In each case, infrared signals are detected by trigeminal nerve fibres that innervate specialized pit organs on the animal’s face5, 6, 7, 8, 9, 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-specific or cell-type-specific manner. Previously, we have shown that snakes co-opt a non-heat-sensitive channel, vertebrate TRPA1 (transient receptor potential cation channel A1), to produce an infrared detector6. Here we show that vampire bats tune a channel that is already heat-sensitive, TRPV1, by lowering its thermal activation threshold to about 30°C. This is achieved through alternative splicing of TRPV1 transcripts to produce a channel with a truncated carboxy-terminal cytoplasmic domain. These splicing events occur exclusively in trigeminal ganglia, and not in dorsal root ganglia, 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 novel molecular mechanism for physiological tuning of thermosensory nerve fibres.

At a glance


  1. Anatomy of fruit bat and vampire bat sensory ganglia.
    Figure 1: Anatomy of fruit bat and vampire bat sensory ganglia.

    a, Facial anatomy of fruit bat (left) and vampire bat (right). Red arrowheads mark pit organs surrounding the vampire bat’s nose. b, Neuronal cell sizes determined from histological sections of fruit bat TG (n = 300, 7 independent sections), fruit bat DRG (n = 345, 9 sections), vampire bat TG (n = 164, 6 sections) and vampire bat DRG (n = 400, 11 sections).

  2. Sequence and distribution of vampire bat TRPV1.
    Figure 2: Sequence and distribution of vampire bat TRPV1.

    a, Deduced protein sequences for TRPV1 short (TRPV1-S) and long (TRPV1-L) isoforms from vampire bat sensory ganglia. b, Abundance of TRPV1 isoform transcripts in vampire and fruit bat sensory ganglia as determined by transcriptome profiling and/or direct sequencing of RT–PCR products (≥86 clones) amplified from sensory ganglia mRNA. c, In situ hybridization, showing expression of TRPV1 and TRPA1 transcripts in histological sections from vampire bat TG or DRG (scale bar, 50 μm). d, Prevalence of TRPV1 or TRPA1 mRNA expression within vampire bat TG or DRG (mean±s.e.m.). Data derived from n = 554 neurons, 14 sections for V1-TG; 783 neurons, 17 sections for A1-TG; 1,455 neurons, 15 sections for V1-DRG; and 1,030 neurons, 10 sections for A1-DRG.

  3. Functional analyses of vampire bat TRPV1 isoforms.
    Figure 3: Functional analyses of vampire bat TRPV1 isoforms.

    a, HEK293 cells expressing vampire bat TRPV1 isoforms were analysed for heat or capsaicin (10μM)-evoked responses using calcium imaging; colour bar indicates relative change in fluorescence ratio, with purple and white denoting lowest and highest cytoplasmic calcium, respectively (n141 cells per channel). Average temperature-response profiles for capsaicin-sensitive cells are shown at right. b, Arrhenius plots show thermal thresholds and Q10 values for baseline and evoked responses for TRPV1-S and TRPV1-L (+80mV, n = 8). c, Relative heat response profiles of vampire bat TRPV1 isoforms compared with rat TRPV1, as measured electrophysiologically in oocytes (response at each temperature was normalized to maximal response at 48°C; VH = −80mV, n8). Data show mean±s.d.

  4. Genomic organization of mammalian Trpv1 locus.
    Figure 4: Genomic organization of mammalian Trpv1 locus.

    a, Schematic of Trpv1 gene locus spanning putative exons 14 and 15 in animals of Laurasiatheria, Rodentia and Primate groups. Splicing events between exons 14 (blue) and 15 (black) are shown, including those involving exon 14a (red). Thermal activation thresholds for resulting channel isoforms are shown at right (n.d., not determined). Lengths of intronic region and relative positions of exon 14a are indicated. b, Consensus phylogenetic tree from Bayesian estimation, with clade credibility values shown for branches with <100% support. c, d, Structures of mini-genes (top) used for in vivo splicing assay in HEK293 cells, showing location of CMV promoter and polyadenylation site (pA), defining start and end of transcribed unit. Reverse transcripts were generated with primers annealing to 3′ vector sequence (1) or oligo-dT (2), as indicated, and products amplified with T7 and primer (1) pair. Reaction products were resolved on agarose gel (middle) and major bands collected for characterization of splicing products (bottom).


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Author information

  1. These authors contributed equally to this work.

    • Elena O. Gracheva &
    • Julio F. Cordero-Morales


  1. Department of Physiology, University of California, San Francisco, California 94158-2517, USA

    • Elena O. Gracheva,
    • Julio F. Cordero-Morales &
    • David Julius
  2. Centro de Ecología, Laboratorio de Biología de Organismos, Instituto Venezolano de Investigaciones Científicas (IVIC), Caracas 1020-A, Venezuela

    • José A. González-Carcacía &
    • Carla I. Aranguren
  3. Department of Embryology, Carnegie Institution, Baltimore, Maryland 21218, USA

    • Nicholas T. Ingolia
  4. Centro de Biofísica y Bioquímica, Laboratorio de Fisiología Celular, Instituto Venezolano de Investigaciones Científicas (IVIC), Caracas 1020-A, Venezuela

    • Carlo Manno
  5. Department of Cellular and Molecular Pharmacology, University of California, San Francisco, California 94158-2517, USA

    • Jonathan S. Weissman &
    • David Julius
  6. California Institute for Quantitative Biosciences, University of California, San Francisco, California 94158-2517, USA

    • Jonathan S. Weissman
  7. Howard Hughes Medical Institute, University of California, San Francisco, California 94158-2517, USA

    • Jonathan S. Weissman


E.O.G., J.F.C.-M. and N.T.I. designed and performed experiments and analysed data. N.T.I. and J.S.W. developed analytical tools and analysed data. J.A.G.-C., C.I.A. and C.M. collected bat species and obtained tissues for analysis. E.O.G., J.F.C.-M. and D.J. wrote the manuscript with discussion and contributions from all authors. J.S.W. and D.J. provided advice and guidance throughout.

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The authors declare no competing financial interests.

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Deep sequencing data are archived under GEO accession number GSE28243. GenBank accession numbers are JN006855 (D. rotundus TRPV1-S), JN006856 (D. rotundus TRPV1-L), JN006857 (D. rotundus TRPA1), JN006858 (C. brevicauda TRPA1), JN006859 (C. brevicauda TRPV1-L), JN006860 (C. brevicauda TRPV1-S), JN006861 (Scapanus orarius TRPV1-L), JN006862 (S. orarius TRPV1-S), JN006863 (Pteropus rodricensis intron), JN006864 (D. rotundus intron), JN006865 (C. brevicauda intron), JN006866 (P. vampyrus intron), JN006867 (Rousettus aegyptiacus intron) and JN006868 (S. orarius intron).

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