Primary processes in sensory cells: current advances
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In the course of evolution, the strong and unremitting selective pressure on sensory performance has driven the acuity of sensory organs to its physical limits. As a consequence, the study of primary sensory processes illustrates impressively how far a physiological function can be improved if the survival of a species depends on it. Sensory cells that detect single-photons, single molecules, mechanical motions on a nanometer scale, or incredibly small fluctuations of electromagnetic fields have fascinated physiologists for a long time. It is a great challenge to understand the primary sensory processes on a molecular level. This review points out some important recent developments in the search for primary processes in sensory cells that mediate touch perception, hearing, vision, taste, olfaction, as well as the analysis of light polarization and the orientation in the Earth’s magnetic field. The data are screened for common transduction strategies and common transduction molecules, an aspect that may be helpful for researchers in the field.
KeywordsMechanoreception Photoreception Taste Olfaction Magnetoreception
Channel cyclic nucleotide-gated channel
Epithelial sodium channel
Glutamic acid-rich protein
GTP-binding protein coupled receptor
Inner hair cell
Inactivation no after-potential D
Mechanosensitive channel-related protein
Outer hair cell
Olfactory receptor neuron
Domain postsynaptic density/discs-large/zonula occludens domain
Channel transient receptor potential channel
Sensory cells provide the central nervous system with vital information about the body and its environment. Each sensory cell detects specific stimuli using highly specialized structures which operate as sensors for adequate stimuli. Thus, the posture of the body, its supply with nutrients and oxygen, the state of the cardiovascular and digestive systems, as well as the body temperature and ion concentrations are constantly monitored by a set of sensory cells. Moreover, information about objects in the environment, their shape, color, chemical composition, their distance and movement are collected and conveyed to the central nervous system. This steady and complex flow of coded information is then integrated and used to generate sensible behavior.
Sensory cells display a multitude of remarkable adaptations towards their tasks. The adequate stimulus is detected by a sensor which must be both selective and sensitive. To detect weak stimuli that transfer only little energy to the sensory cell, primary signals have to be amplified and an output signal must be generated that can be interpreted by the brain. These primary processes constitute an efficient and characteristic transduction cascade in each type of sensory cell. In the evolution of animals, sensory acuity is continuously sharpened under intense selective pressure, and the transduction cascades are the prime targets of this process. The result is a set of cells with astonishing performance: photoreceptors that detect single-photons, mechanoreceptors that respond to the movements on a nanometer scale and chemoreceptors that report the detection of single molecules. Furthermore, the perception of electromagnetic radiation by many animal species amazes physiologists, and the research for the transduction mechanisms that mediate the analysis of infrared radiation, electrical fields or magnetic navigation cues is among the most exciting fields in sensory physiology. This review tries to provide a brief overview of current work on sensory transduction mechanisms. I focus on just one or a few research topics in each of the sensory modalities, and I try to point out the significance of recent findings for the scientific concepts of sensory function. The depth of knowledge and the accuracy of mechanistic models vary considerably between well-studied cells such as photoreceptors and more enigmatic cells like the touch receptors in the human skin. However, as common transduction features begin to appear, new experimental approaches become available which are based on the observation that various sensory cells use similar or homologous proteins for transduction. Thus, the examination of transduction channels or amplification mechanisms in one type of sensory cell may help to advance studies of transduction in a different modality. The present review is designed to promote such effects.
Mechanoreceptors: tugging at enigmatic channels
Mechanoreceptors in vertebrates are much less well understood, and there is a hope that the C. elegans touch receptor neuron will serve as a blueprint for a corresponding model composed of homologous vertebrate proteins. This approach has only just begun, but there are already promising results. A member of the PHB domain protein family, stomatin-like protein 3 (SLP3), turned out to be necessary for normal touch sensation in mice (Wetzel et al. 2007). The related protein stomatin is needed for sensory function in rapidly adapting D-hair mechanoreceptors (Martinez-Salgado et al. 2007). These findings suggest that SLP3 and stomatin play a similar role in vertebrate mechanotransduction as MEC-2 plays in the C. elegans touch receptor. Although it is too early to speculate the notion that vertebrate mechanotransducers are protein complexes with tethered transduction channels appears to be a reasonable working hypothesis. Future work may lead to the identification of multiple transduction components and to gene ablation experiments with unambiguous phenotypes. Up to now, the search for mechanotransduction channels has only produced conflicting results (Drew et al. 2004; Gottlieb et al. 2008), and the molecular identity of the channels remains elusive. An important question is whether low-threshold touch receptors and high-threshold nociceptors use the same gating principle to generate mechanoreceptor potentials (Hu et al. 2006). A recent report on the effects on pain behavior of a spider toxin that blocks stretch-activated cation channels (GsMTx4; Park et al. 2008) suggested an involvement of transduction channels gated by membrane stretch. It is conceivable, although entirely speculative, that the detection of gentle touch relies on multi-protein transduction complexes in vertebrate touch receptor neurons, while nociceptors respond to their much stronger stimuli with simple stretch-sensitive channels. It is also possible that the C. elegans-type transduction complex and the stretch-sensitive channel do not represent mutually exclusive gating principles. There may be various intermediate structures with transduction channels attached to the cytoskeleton or to proteins in the membrane or the extracellular matrix. The challenge is to identify the channel protein itself, which can probably be done only by genetic means, because the proteins cannot be isolated from the fine sensory endings of mechanoreceptors. Once this is achieved, auxiliary subunits and associated proteins can be identified more easily.
A fascinating example of vertebrate mechanosensory transduction by tethered channels is the generation of receptor potentials in the hair cells of the inner ear. These exquisitely sensitive cells detect movements on a nanometer scale by their apical hair bundles and transmit the sensory signal to afferent neurons with high efficiency. Based on groundbreaking electrophysiological studies (Corey and Hudspeth 1979; Hudspeth 1982; Corey and Hudspeth 1983) and the discovery of protein filaments connecting the sterocilia within a hair bundle (Pickles et al. 1984; Furness and Hackney 1985), a working hypothesis was formulated that explained hair-cell function in terms of a tethered transduction channel (Pickles 1985; Holton and Hudspeth 1986; Hudspeth 1989). An impressive array of excellent biophysical investigations was since carried out to scrutinize and improve this hypothesis (recent reviews: Gillespie et al. 2005; Corey 2006; Fettiplace and Hackney 2006; Ricci et al. 2006; Grant and Fuchs 2007; Vollrath et al. 2007). Today, the tethered-channel hypothesis is well established, and much of the current work is focussed on identifying the molecular components of the transduction complex.
Much effort has been invested into the search for the molecular identity of the transduction channels that sit at one or both ends of the tip link. For each candidate channel protein, the expression at the tip of the stereocilia must be demonstrated, and it must be shown that the channel is gated by hair-bundle displacements. Moreover, ablation of the candidate gene must cause cochlear and vestibular dysfunction. The first promising candidate was the ion channel TRPN1. Gene silencing experiments caused the expected phenotypes in zebrafish (Sidi et al. 2003). However, TRPN1 was found to be expressed in the kinocilia of lower vertebrates, and not in the stereocilia (Shin et al. 2005), and the trpn1 gene is not present in avian and mammalian genomes. A number of other proteins have been investigated as possible candidates for the hair cell transduction channel, including TRPA1, TRPML3, TRPV4, and TMHS (reviewed in Corey 2006; Cuajungco et al. 2007; Vollrath et al. 2007). But the channel has not been identified to date, and the search for the tethered channels of the inner ear remains one of the most urgent challenges in sensory physiology.
The primary transduction process in hair cells requires a complex dynamic environment to function properly. To generate neuronal signals upon detecting a very faint sound (the detection threshold in humans is ~10−16 W/cm2), and to discriminate frequencies over a range of three orders of magnitude (20-20 kHz), the Corti organ must amplify the primary signal. Research in cochlear amplification has seen exciting advances in recent years. I will only briefly outline this topic here, as it is more an auxiliary than a primary process. Amplification of the primary signal, which are local vibrations of the Corti organ due to resonance, is performed by the outer hair cells (OHCs) of the Corti organ (reviews: Fettiplace and Hackney 2006; Frolenkov 2006; Ren and Gillespie 2007; Ashmore 2008). OHCs possess the unususal (perhaps unique) property of electromotility. They contract upon depolarization, and they elongate upon hyperpolarization. This motorresponse to changes in membrane voltage is extremely rapid. An OHC can go through tens of thousands of contraction/elongation cycles per second and can thus follow the vibration frequency caused by resonance at any particular spot along the cochlear. Importantly, the stereocilia of OHCs are embedded in the tectorial membrane (Fig. 2a) and, thus, constitute a mechanical link between the sensory epithelium and the tectorial membrane. As the OHCs oscillate, they “shake” the entire structure at the point of resonance and amplify the local movement of endolymph that stimulates the sensory IHCs. In mammals, electromotility is mediated by the protein prestin, a membrane protein that changes its volume under the control of the membrane voltage (Zheng et al. 2000; Dallos et al. 2006, 2008). The protein swells by voltage-dependent uptake of chloride ions, a process that is extremely fast. Electromotility is thus the orders of magnitude faster than any motion based on cAMP-consuming motor proteins. The OHCs amplify the primary signal by a factor of 100–1,000 and hence allow the IHCs to operate at the levels of sound pressure that constitute our normal auditory environment.
Phototransduction: dynamic scaffolds
Reversible attachment to a transduction scaffold may constitute an effective mechanism for sensory adaptation. Proteins may be tethered to the signalplex for high sensitivity and may be removed from the complex to reduce sensitivity. This concept arises from the observations of light-induced protein translocation in photoreceptors (Calvert et al. 2006). In both Drosophila and in mouse rod photoreceptors, key members of the phototransduction cascade are shuttled to and from the transduction site in a light-dependent way. The heterotrimeric GTP-binding protein transducin in vertebrates sticks to the disc membrane in the dark by a farnesyl group on its γ subunit and an acyl group on its α subunit. This double-anchor effectively attaches the inactive trimer to the discs. During photoactivation of rhodopsin, however, transducin dissociates into the βγ dimer and the active Gα-GTP, both of which have increased solubility because each has only one membrane anchor. This “photo-solubilization” of transducin releases much of the protein from the disc during intense or prolonged illumination. The soluble protein is able to diffuse to the inner segment where it is sequestered by a still unknown mechanism (Sokolov et al. 2002; Lobanova et al. 2007), until it returns again to the outer segment in the dark. A similar translocation of Gαq is thought to contribute to light-adaptation in the fly photoreceptor (Kosloff et al. 2003). In both cells, G proteins and arrestin—a key protein for response termination—were shown to travel in opposite directions (Lee and Montell 2004; Strissel et al. 2006). Attenuation of the light response is brought about by sequestration of transducin in the inner segment and accumulation of arrestin in the outer segment (Calvert et al. 2006). Such translocation of proteins between the signaling complex and a non-photosensitive compartment is not restricted to soluble proteins. The TRPL channel of fly photoreceptor undergoes a light-dependent, reversible translocation between rhabdomers and cell body (Bähner et al. 2002; Meyer et al. 2006), a process that may involve endocytosis and intracellular transport by motor proteins. Whatever the exact molecular mechanisms of protein translocation are, the data available today clearly show that signaling complexes in photoreceptors can be subject to light-dependent restructuring. Such dynamic regulation of protein networks may have profound effects on transduction efficiency—not only in vision. Once again, the photoreceptor may serve as a model cell for the exploration of new principles in sensory transduction.
Taste transduction: gustatory genetics
The search for transduction mechanisms of sour-sensitive taste cells has been hampered by the fact that the adequate stimulus, protons, affects virtually every protein with amino acid residues that can bind H+. Thus, pH effects can be measured with most channels, transporters and proteins involved in signal transduction, and it is difficult to prove that a pH effect on an individual protein is related to the physiological proton sensor of a sour-selective taste cell. This conundrum is made worse by the fact that protons can reach the basolateral membrane of taste cells through the paracellular pathway, and that protonated acids can cross the plasma membrane and cause intracellular acidification. The actions of pH changes are, therefore, essentially unspecific and not localized. Physiological data, however, show that there is a subpopulation of taste cells equipped with specific pH sensitivity. Such a property could arise from specific expression of proton-gated ion channels and/or by a reduced cytosolic pH buffer capacity. Indeed, intracellular acidification and stimulus-related Ca2+ signals could be demonstrated in a subpopulation of taste cells upon extracellular pH changes (Richter et al. 2003). The most convincing set of evidence for a specific H+ sensor in sour-specific taste cells comes from studies of an ion channel from the TRP family, TRPP3 (synonyms: TRPP3 = PKD2L1; TRPP = polycystin family; Delmas 2005). This protein is expressed in a subset of taste cells that are not sensitive to other taste qualities and, in conjunction with the related protein PKD1L3, confers acid sensitivity when expressed in the cell line HEK 293 (LopezJimenez et al. 2006; Ishimaru et al. 2006; Inada et al. 2008). When TRPP3-expressing taste cells are removed by genetic manipulation, animals do no longer respond to sour stimuli, while the other taste qualities are intact (Huang et al. 2006). While many details of the sour transduction process are not yet clear, these data strongly suggest that TRPP3 is part of the sour taste receptor (Meyerhof 2008).
Salt detection is thought to work through cation ion channels which conduct Na+ or K+ from the surface of the tongue into salt-sensitive cells. In parallel, Cl− ions are thought to take the paracellular route across the taste epithelium (Roper 2007). A candidate for Na+ taste is the amiloride-sensitive epithelial Na+ channel ENaC whose three subunits α, β. and γ are expressed in some taste receptor cells (Lin et al. 1999). Both amiloride-sensitive and amiloride-insensitive components of salt taste were identified by electrophysiology and in the behavioral experiments (Avenet and Lindemann 1991; Shigemura et al. 2008). Amiloride-sensitive, highly Na+-selective channels are present in some taste cells (Sugita 2006). However, the definite answer to the question whether ENaC mediates salt taste must probably await the generation of a taste-cell specific conditional knockout mouse, as global deletions of any of the three ENaC subunits results in perinatal lethality (Hummler and Vallon 2005). Thus, the transduction mechanism of salt taste is presently not well understood.
An important point for the examination of primary processes in taste transduction is to identify the right cell types within a taste bud. Evidence from a number of morphological and physiological studies supports the view that only a subset of cells in the taste bud expresses taste receptors and transduction proteins. Other cells have different functions including synaptic transmission or glia-like supportive function (Roper 2007). At present the data provide a scenario in which taste receptor cells (type II cells; Fig. 5) respond to tastants with the release of ATP, probably through pannexin 1 hemichannels (Finger et al. 2005; Huang et al. 2007). ATP appears to act as paracrine transmitter on type III cells which express P2X2 and P2X3 purinergic receptors and form synapses with afferent neurons (Finger et al. 2005). Finally, type I cells may limit wide-spread diffusion of ATP by an ecto-ATPase (Bartel et al. 2006), thus serving a glia-like function in the taste bud. This working hypothesis of a paracrine transmission system illustrates the complexity of signaling inside a taste bud. Many observations have yet to be integrated into this model. For example, amiloride-sensitive currents are restricted to type I cells (Vandenbeuch et al. 2008) suggesting that these glia-like cells are also responsible for salt taste. Sour taste, in contrast, was localized to the type III cells of the taste bud (Huang et al. 2008; Kataoka et al. 2008). Substantial differences in morphology and expression patterns have been demonstrated between taste buds of rats and mice (Ma et al. 2007) and between different taste buds on the same tongue (Kinnamon et al. 1993; Romanov and Kolesnikov 2006). Moreover, psychophysical effects of peripheral neuromodulators (Heath et al. 2006) have to be examined as they may regulate sensory signal processing in the taste bud.
Olfactory transduction: coping with fuzzy receptors
Thus, in contrast to phototransduction, the metabotropic transduction step on olfactory transduction operates with low efficiency. This point is supported by the consistent observation that odorant concentrations used for physiological experimentation with ORNs have to be in the range of 1-100 μM to detect cAMP synthesis or to record cAMP-dependent receptor currents (Pace et al. 1985; Firestein et al. 1993; Araneda et al. 2000). In fact, metabotropic transduction in ORNs appears to work without any molar amplification: Micromolar concentrations of odorants are needed to generate micromolar concentrations of cAMP in ORNs. The absence of effective metabotropic amplification results directly from the use of low-selectivity receptors which, in turn, is required for a system open to an unlimited range of odorants. How then, can the olfactory system work as the highly sensitive detection system with amazing powers of odor discrimination?
Odorants can be detected at extremely low concentrations, much lower than the 1–100 μM used in physiological experiments on isolated cells. It is difficult to compare results obtained from single ORNs with the performance of the olfactory system in vivo for at least three reasons: (1) ORNs show an extremely high degree of convergence, as roughly 2,000 ORNs are connected with a single mitral cell in the olfactory bulb. It is conceivable that such a large ensemble of afferent neurons causes excitation in a mitral cell even if each individual ORN is only slightly activated. Thus, temporal summation of multiple weak signals may contribute to olfactory sensitivity. (2) The sensory membrane of ORNs is embedded in a mucus layer that, in terrestrial animals, contains high concentrations of odorant-binding proteins (Pelosi 2001; Pelosi et al. 2006; Ko and Park 2008; Laughlin et al. 2008). These small, soluble proteins belong to the lipocalin-family, proteins that can shuttle hydrophobic molecules through body fluids and across cell membranes. In the olfactory mucus, these binding proteins display odor-specificity (Löbel et al. 2002) and can interact with odorant receptor proteins (Matarazzo et al. 2002). The precise role of these proteins in olfaction is not understood, but they are expected to influence the interaction between odorants and their receptors. (3) ORNs possess an unusual signal amplification mechanism that boosts the odor-induced depolarization and may be critical for responses to weak stimuli. This mechanism utilizes the Ca2+ influx through cAMP-gated transduction channels in the chemosensory membrane (Fig. 7). Ca2+ opens chloride channels which conduct a depolarizing efflux of chloride ions (Kleene and Gesteland 1991). The anion influx strongly amplifies the receptor potential and depolarizes the ORNs sufficiently for excitation (Kurahashi and Yau 1993; Lowe and Gold 1993; Kleene 1997). To support this excitatory chloride current, ORNs accumulate chloride and support an elevated intracellular chloride concentration (Reuter et al. 1998; Kaneko et al. 2004). Current research efforts in this field focus on the molecular identification of the calcium-dependent chloride channels (Reisert et al. 2003; Kaneko et al. 2006; Pifferi et al. 2006; Caputo et al. 2008; Schroeder et al. 2008; Yang et al. 2008) and on the mechanisms of chloride homeostasis that support this signal amplification (Reisert et al. 2005; Nickell et al. 2007; Smith et al. 2008).
While ORNs have to operate with low selectivity, pheromone receptors in the vomeronasal organ display a high degree of specificity and sensitivity for the chemical compounds that orchestrate reproductive behavior among the members of a species. Consequently, the primary processes are fundamentally different between these two sensory modalities. The prototypical pheromone receptors of the silk moth Bombyx mori basically respond to single pheromone-binding events, although the exact nature of this process and, in particular, the role of pheromone-binding proteins is still not fully understood (Kaissling 2001). But mammalian pheromone detectors are highly sensitive as well. Studies of pheromone receptors in the mouse vomeronasal organ (VNO) revealed detection thresholds near 10−11 M for the neuronal response (Leinders-Zufall et al. 2000). VNO neurons employ two distinct sets of pheromone receptors, the V1R and V2R families, each of which comprises 100–200 different receptors (Dulac and Wagner 2006; Zufall and Leinders-Zufall 2007; Dulac and Kimchi 2008). The V1R family recognizes small urinary molecules that act as pheromones in mammals. Each V1R neuron seems to express only a single member of the V1R receptor family and, consequently, displays high pheromone specificity. A separate population of VNO neurons expresses V2R genes. These cells respond to urinary peptides, in particular to major histocompatibility complex (MHC) class 1 peptides (Leinders-Zufall et al. 2004) and help conspecific animals to gain information related to the immune system of their mates. The transduction cascade used by both V1R and V2R neurons is also different from that operating in ORNs. Phospholipase C is believed to be the target enzyme, releasing IP3, Ca2+, DAG and polyunsaturated fatty acids (PUFA) as second messengers upon pheromone stimulation (Liman and Zufall 2004). Robust evidence is available for a central role of the protein TRPC2 as transduction channel (Zufall et al. 2005). TRPC2 is expressed in the chemosensory microvilli of VNO neurons (Liman 1999), the channel is gated by DAG (Lucas et al. 2003), and TRPC2 knock-out mice lose the ability to distinguish between male and female conspecifics (Stowers et al. 2002; Leypold et al. 2002; Kimchi et al. 2007). Nevertheless, some aspects of pheromone-driven behavior remain intact in the TRPC2−/− mice, in particular the detection of MHC 1 peptides (Kelliher et al. 2006). This finding suggests that a different population of VNO neurons exists which does not use TRPC2 as transduction channel.
Intense examination of the VNO and the olfactory epithelium currently challenges the traditional view that the two systems are dedicated exclusively to two discrete functions, namely pheromone control and olfaction (Spehr et al. 2006). It becomes clear that both systems contain various different populations of neurons, each with a specific purpose and specific molecular equipment. The characterization of these chemosensory cells and their sensory function is an exciting task for sensory physiologists (Elsaesser et al. 2005; Liberles and Buck 2006; Leinders-Zufall et al. 2007).
Evaluating electromagnetic fields: more primary processes
In addition to analyzing the intensity and wavelength of visible light, animals can extract vital information from the degree of light polarization, from infrared radiation, as well as from electrical fields and from the Earth’s magnetic field. Exciting recent developments have yielded insights into some amazing primary processes that mediate these tasks. I will briefly review progress in polarization vision and magnetoreception. For the topics of electroreception and infrared perception, I refer the reader to a set of excellent reviews recently published in this journal (Bleckmann et al. 2004; von der Emde 2006; Caputi and Budelli 2006).
Light polarization is not an exotic phenomenon to most of us, as we are used to polarizing filters on our cameras and our sunglasses, and the perception of light polarization appears to be just an additional aspect of vision. Magnetoreception, however, is a different matter. It is utterly amazing to observe the navigational skills of migratory animals and their use of magnetic cues. While human travellers need to be equipped with the Global Positioning System (GPS), a good map, a compass, and some geographic knowledge to find their way, animals apparently “see” or “feel” the geomagnetic field and know how to use the magneto-sensory perception to travel over long distances. Two questions have to be addressed for navigation: Where am I? And which direction leads to my destination? Interestingly, animals seem to use different sensory strategies to obtain these informations, involving different primary processes (Johnsen and Lohmann 2005; Mouritsen and Ritz 2005; Wiltschko and Wiltschko 2005, 2006, 2007). Animals can exploit at least three parameters of the magnetic field: the inclination of the magnetic field relative to the Earth’s surface, and the direction to magnetic north, parameters that we obtain from an inclination compass and a declination compass, respectively. Moreover, animals perceive the local intensity of the geomagnetic field, a parameter that we determine using a magnetometer. In the search for the primary processes that transduce these parameters into neuronal signals, two models are currently favored, the radical pair model and the magnetite hypothesis. The radical pair model is based on the observations that certain modes of magnetoreception are light-dependent (Ritz et al. 2002), and that chemical free-radical reactions can be influenced by magnetic fields of ≤50 μT, the intensity of the geomagnetic field (Maeda et al. 2008). The candidate biomolecule for such a light-induced, magneto-sensitive free-radical reaction is cryptochrome, a photopigment that is present in the retina of migratory birds (Möller et al. 2004) and was found to be necessary for magnetoreception in Drosophila (Gegear et al. 2008). Cryptochrome absorbs blue light and forms long-lived radical pairs (Liedvogel et al. 2007). The light-dependence of magnetoreception in birds has given rise to the notion that the impact of the magnetic field on cryptochrome photochemistry may represent a primary sensory process (Ritz et al. 2000, 2004; Beason 2005; Wiltschko and Wiltschko 2007). The idea is that cryptochrome forms a singlet radical pair upon illumination, and that the kinetics of singlet/triplet interconversion is affected by the geomagnetic field (Fig. 8b). The balance between singlet products and triplet products depends to some extent on the orientation of a cryptochrome-containing cell in the geomagnetic field. If a cryptochrome-containing cell is able to compare the amount of chemical products resulting from singlet pairs to that originating from triplet pairs, it can determine the yield of spin interconversion. Ritz et al. (2000) proposed that a visual representation of the magnetic field can result from an ordered distribution of cryptochrome-containing cells in the retina. While the radical pair model has not been established in all details, it represents a valuable hypothesis for directional magnetoreception in birds—it provides the molecular concept for a visual compass in the birds’ eyes (Wiltschko and Wiltschko 2006).
But a compass alone does not bring you home if you do not know where you are. Thus, positional information is needed for navigation, information of the kind that we derive from comparing GPS readings with a map. Behavioral studies have revealed that migrating animals (birds, sea turtles, spiny lobsters) indeed possess positional information, and that this information is derived from the geomagnetic field (Lohmann et al. 2007). The inclination and the local intensity of the magnetic field supply useful positional information for large areas of the globe. For example, each location in the atlantic ocean has a unique combination of inclination and intensity, as the lines of equal field inclination (isoclinics) are oriented roughly east-to-west, while the lines of equal field intensity (isodynamics) run roughly north-to-south. Isoclinics and isodynamics thus form a grid on a magnetic map, just like latitudes and longitudes do on a geographic map. There is strong evidence that migratory animals can follow both isoclinics (Lohmann and Lohmann 2006) and isodynamics (Dennis et al. 2007) and, therefore, must have the ability to gain and process positional information. The primary processes underlying positional magnetoreception are thought to be distinct from the ones described by the radical pair model. The magnetite hypothesis was originally based on the microbiology of magnetotactic bacteria. These microorganisms contain strings of magnetite (Fe3O4) particles, each of which has a size of 30–120 nm, and is a stable, single-domain magnetic dipole (Blakemore 1982; Schüler 2008). The strings restrain thermal movements of the individual particles, so that their magnetic moments add up, and the entire string tends to align with the geomagnetic field, just like a compass needle. Animal physiologists have long speculated that magnetite particles may transduce geomagnetic signals in migratory animals (Kirschvink and Gould 1981; Kirschvink et al. 2001; Walker et al. 2002). Strings of permanently magnetic particles may be connected to the gating mechanism of an ion channel so that the magnetic field can trigger channel opening and generate a receptor potential (Fig. 8c). Indeed, single-domain magnetite particles were discovered in fish (Diebel et al. 2000), and indirect evidence points to a role of single-domain magnetite in magnetoreception by mole rats (Wegner et al. 2006) and bats (Holland et al. 2008). Curiously, the magnetite particles in various animals with robust magnetoreception are very small and are not aligned in orderly chains (e.g., homing pigeon; Fleissner et al. 2003). These particles have no stable magnetic moment, but they can assume a magnetic polarization in an applied field. An important recent finding is that such superparamagnetic material can, in principle, serve as a sensor in magnetosensory cells. Clusters of these particles change their shape when they are moved within a magnetic field (Fig. 8c). And the resulting forces are sufficient to gate ion channels (Fleissner et al. 2007; Hsu et al. 2007; Solov’yov and Greiner 2007). Thus, cryptochrome and magnetite may be the transducing molecules in directional and positional magnetoreception. This concept will be scrutinized and extended in the coming years with the still distant goal to understand magneto-electrical transduction in sensory neurons.
The data collected in this review illustrate several prominent similarities between primary processes of different sensory modalities:
(1) Stimulus detection: G-protein coupled receptors (GPCRs) detect a wide spectrum of chemical and visual stimuli. At least five families of GPCRs mediate chemosensory qualities and a number of rhodopsin varieties cover the visual and ultraviolet spectra. Mechanodetectors directly couple movement to the opening of transduction channels. (2) Transduction channels: most transduction channels belong to one of three protein superfamilies, die TRPs, the CNGs, and the degenerins. These are mostly non-selective cation channels, which are Ca2+-permeable and show little voltage dependence. Transduction channels are often components of a supramolecular protein complex that regulates channel activity. (3) Transduction complex: a large set of proteins may co-assemble to form a transduction complex. The considerable plasticity of a transduction complex may underly adaptation, sensitization, response kinetics, and noise reduction. (4) Amplification: primary receptor potentials may be amplified by prolonged activation of metabotropic receptors, by large electrochemical gradients for the receptor current, or by secondary currents that are conducted by distinct sets of ion channels.
These common principles may also apply to primary processes in sensory cells where transduction mechanisms are not yet understood.
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