TRPA1 is a candidate for the mechanosensitive transduction channel of vertebrate hair cells

Corey, David P.; Garcı́a-Añoveros, Jaime; Holt, Jeffrey R.; Kwan, Kelvin Y.; Lin, Shuh Yow; Vollrath, Melissa A.; Amalfitano, Andrea; Cheung, Eunice L M; Derfler, Bruce; Duggan, Anne; Géléoc, Gwenaëlle S. G.; Gray, Paul A.; Hoffman, Matthew P.; Rehm, Heidi L.; Tamasauskas, Daniel; Zhang, Duan Sun

doi:10.1038/nature03066

Cited by 649 publications

(518 citation statements)

References 42 publications

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“…Electrophysiological studies also report aminoglycoside blockade of DRG neurons that may account for cases of aminoglycosideinduced analgesia of pain receptors (Raisinghani and Premkumar, 2005;Zhou and Zhao, 2002;Zhou et al, 2001). Hair cells and kidney cells also express a variety of transient receptor potential (TRP) channels which allow the uptake of large organic molecules, including aminoglycosides (Corey et al, 2004;Hellwig et al, 2004;Liedtke et al, 2000;Marcotti et al, 2005;Meyers et al, 2003;Raisinghani and Premkumar, 2005;Strotmann et al, 2000;Xu et al, 2002;Zheng et al, 2003). Thus, the uptake of GTTR into cells through aminoglycosidepermissive cation channels is likely to lead to diffuse cytoplasmic labeling.…”

Section: Other Sensory Locations and Mechanisms Of Uptakementioning

confidence: 99%

Uptake of fluorescent gentamicin by vertebrate sensory cells in vivo

et al. 2006

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Aminoglycoside uptake in the inner ear remains poorly understood. We subcutaneously injected a fluorescently-conjugated aminoglycoside, gentamicin-Texas Red (GTTR), to investigate the in vivo uptake of GTTR in the inner ear of several vertebrates, and in various murine sensory cells using confocal microscopy.In bullfrogs, GTTR uptake was prominent in mature hair cells, but not in immature hair cells. Avian hair cells accrued GTTR more rapidly at the base of the basilar papilla. GTTR was associated with the hair bundle; and, in guinea pigs and mice, somatic GTTR fluorescence was initially diffuse before punctate (endosomal) fluorescence could be observed. A baso-apical gradient of intracellular GTTR uptake in guinea pig cochleae could only be detected at early time points (<3 h). In 21−28 day mice, cochlear GTTR uptake was greatly reduced compared to guinea pigs, 6-day-old mice, or mice treated with ethacrynic acid. In mice, GTTR was also rapidly taken up, and retained, in the kidney, dorsal root and trigeminal ganglia. In linguinal and vibrissal tissues rapid GTTR uptake cleared over a period of several days.The preferential uptake of GTTR by mature saccular, and proximal hair cells resembles the pattern of aminoglycoside-induced hair cell death in bullfrogs and chicks. Differences in the degree of GTTR uptake in hair cells of different species suggests variation in serum levels, clearance rates from serum, and/or the developmental and functional integrity of the blood-labyrinth barrier. GTTR uptake by hair cells in vivo suggests that GTTR has potential to elucidate aminoglycoside transport mechanisms into the inner ear, and as a bio-tracer for in vivo pharmacokinetic studies.

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Section: Other Sensory Locations and Mechanisms Of Uptakementioning

confidence: 99%

Uptake of fluorescent gentamicin by vertebrate sensory cells in vivo

et al. 2006

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“…The TRPA1 channel, which has 17 ankyrin repeats, is expressed in mammalian inner ear hair cells, making it a tantalizing candidate for the mechanosensitive channel responsible for hearing. 30 However, the TRPA1 knock-out mice are not hearing-impaired, 31,32 although the knock-out strategies, which eliminated the pore segment, leave open the remote possibility that other portions of the protein (including the ankyrin repeats) are the essential parts for TRPA1 function in hearing. Although interest in TRPA1 as the potential mechanotransducer channel in hearing is waning, TRPA1 is clearly implicated in mechanosensation in mice and C. elegans.…”

Section: Ankyrin Repeats As Springs?mentioning

confidence: 99%

A primer on ankyrin repeat function in TRP channels and beyond

2008

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Transient Receptor Potential (TRP) channels are rapidly gaining attention as important receptors and transducers of diverse sensory and environmental cues. Recent progress in the field has provided new insights into the structure and function of the ankyrin repeat motifs present in the Nterminal cytosolic domain of many TRP channels. The topics addressed in this review include the structural features of canonical ankyrin repeats, new clues into the functions these repeats perform in cells, and how this information can be applied to develop further experiments on TRP channels and other proteins containing ankyrin repeats.TRP proteins form a large family of ion channels particularly important in animals from worms to man, with more than 30 members in mammals. 1 The founding family member, the Drosophila trp gene -named for the "transient receptor potential" phenotype its mutation causes in light perception by photoreceptors -was first cloned in 1989. 2 The functions assigned to TRP channels in physiology are constantly expanding. They are key transducers of sensory signals, and are generally important in sensing information about the environment in both neuronal and non-neuronal cells (see ref. 3 for comprehensive reviews). Some TRP channels are found in excitable cells of the sensory nervous system, while others are expressed in various other tissues and organs. TRP channels have been implicated in many physiological processes, including calcium and magnesium homeostasis, neuronal growth, temperature sensation and pain perception, to name a few. For example, TRPV1 senses painfully hot temperatures, low extracellular pH and the capsaicin of "hot" chili peppers, while TRPA1 senses many painful chemical stimuli, including the pungent compounds in wasabi and cinnamon. TRPV1 and TRPA1 are expressed in partially overlapping sets of nociceptor neurons that transmit pain signals to the brain.At a molecular level, TRP channels assemble as tetramers through a channel domain that spans the membrane six times and has sequence similarity to voltage-gated ion channels. TRP channels also have large N-and C-terminal cytosolic domains that flank the transmembrane channel domain. These cytosolic domains participate in channel gating and regulation and sense information about the cellular state -ion and metabolite levels, for example. The TRP channel family is divided into seven subfamilies based on sequence similarity 1 : TRPA (ankyrin), TRPC (canonical), TRPM (melastatin), TRPML (mucolipin), TRPP (polycystin), TRPV (vanilloid), and TRPN (NOMPC). Several of these subfamilies -TRPA, TRPC, TRPN and TRPV -have ankyrin repeat sequence motifs in their N-terminal cytosolic domains. Recent work from my lab and others has taken a structural biology approach to elucidate the roles of these ankyrin repeats in TRP channel function. [4][5][6][7][8][9] The emerging structural and functional features of these TRP channel ankyrin repeats are the focus of this short review. NIH Public Access Ankyrin repeats and their structureAnkyrin rep...

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“…A very interesting hypothesis for the functional role for the 29 ANK repeat containing Drosophila NOMPC channel is that this repeat structure forms the gating spring of mechanoreceptors (Howard and Bechstedt 2004). Vertebrate TRPA1 channels that are candidates for the mechanosensitive transduction channel of hair cells only contain 17 ANK repeats, which may still confer sufficient gating spring stiffness (Corey et al 2004). …”

Section: Ankyrin Repeatsmentioning

confidence: 99%

Structure-function analysis of TRPV channels

Niemeyer

2005

Naunyn-Schmiedeberg's Arch Pharmacol

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In recent years many new members of the family of TRP ion channels have been identified. These channels are classified into several subgroups and participate in many sensory and physiological functions. TRPV channels are important for the perception of pain, temperature sensing, osmotic regulation, and maintenance of calcium homeostasis, and much recent research concerns the identification of protein domains involved in mediating specific channel functions. Recent literature on TRPV channel subunit composition, protein domains required for subunit assembly, trafficking, and regulation will be reviewed and discussed.

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TRPA1 is a candidate for the mechanosensitive transduction channel of vertebrate hair cells

Cited by 649 publications

References 42 publications

Uptake of fluorescent gentamicin by vertebrate sensory cells in vivo

Uptake of fluorescent gentamicin by vertebrate sensory cells in vivo

A primer on ankyrin repeat function in TRP channels and beyond

Structure-function analysis of TRPV channels

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