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TRPA1 in Auditory and Nociceptive Organs.


In: Liedtke WB1, Heller S2, editors.


TRP Ion Channel Function in Sensory Transduction and Cellular Signaling Cascades. Boca Raton (FL): CRC Press/Taylor & Francis; 2007. Chapter 12.
Frontiers in Neuroscience.

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Duke University Medical Center, Durham, North Carolina
Stanford University School of Medicine, Stanford, California
Northwestern University


TRPA1, initially called P120 and ANKTM1, was originally described as a down-regulated protein in mesenchymal tumor cells and was detected in cultured fibroblasts but lost upon oncogenic transformation, although no expression in healthy tissues was described (Schenker and Trueb, 1998; Jaquemar et al., 1999). With in situ hibridization, we found mouse TRPA1 mRNA absent from most major organs (brain, heart, liver, kidneys, skeletal muscles, lungs, spleen, and testes, as well as whisker pad skin and superior cervical ganglia), but present in the inner ear and in certain peripheral sensory ganglia: dorsal root (DRG), trigeminal (TG), and nodose (Nagata et al., 2005). This very restricted pattern of expression suggests specific roles unique to sensory function. Molecularly, TRPA1 has six membrane-spanning domains and a presumed pore-forming domain characteristic of all TRPs and many other ion channels. Its N- and C-terminal segments are predicted to be cytoplasmic. In addition, a distinguishing feature of TRPA1 is a very long N-terminus with up to 17 predicted ankyrin (ANK) repeats (Figure 12.1). Many similar repeats are present in the protein ankyrin, and 29 of them are present in TRPN1, a mechanosensory channel protein of flies, worms, and fish that has not been found in mammals (Walker et al., 2000; Sidi et al., 2003; Li et al., 2006). ANK repeats may serve at least two functions: (1) to interact with other proteins, particularly those of the cytoskeleton, and (2) to provide elasticity when in tandem, forming a molecular spring (cited as V. Bennet, personal communication, in Corey et al., 2004; Howard and Bechstedt, 2004; Sotomayor et al., 2005; Lee et al., 2006). Because many models of mechanically gated channels postulate linkage to a force-transducing structure like the cytoskeleton or an elastic gating spring (García-Añoveros and Corey, 1997; Gillespie and Walker, 2001), channels like TRPN1 and TRPA1 may be well endowed for the mechanical transduction that characterizes the auditory and vestibular organs as well as the somatosensory and autonomic ganglia that express it. Based on the hypothesis that the transduction channel of hair cells and somatosensory neurons could be a TRP channel (Duggan et al., 2000), we screened (RT-PCR and in situ hybridization) TRP genes for expression in the inner ear and somatosensory ganglia. We found several TRPs expressed in ganglia and two whose mRNA is expressed in the organ of Corti, the place in the cochlea where the sensory cells reside (unpublished results and Corey et al., 2004). In addition, a third TRP channel protein (MCOLN3, or TRPML3) has also been detected in hair cells (Di Palma et al., 2002). In this chapter we discuss TRPA1, which is expressed both in the inner ear and peripheral ganglia.

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