PERSPECTIVE ARTICLE
published: 26 October 2012
doi: 10.3389/fncel.2012.00048
Functional and evolutionary aspects of chemoreceptors
Dieter Wicher*
Department of Evolutionary Neuroethology, Max Planck Institute for Chemical Ecology, Jena, Germany
Edited by:
Michael Hausser, University College
London, UK
Reviewed by:
Mala Shah, University of London, UK
Jean-Pierre Montmayeur, The
Coca-Cola Company, USA
*Correspondence:
Dieter Wicher, Department of
Evolutionary Neuroethology, Max
Planck Institute for Chemical
Ecology, Hans-Knöll-St. 8, D-07745
Jena, Germany.
e-mail: dwicher@ice.mpg.de
The perception and processing of chemical signals from the environment is essential for
any living systems and is most probably the first sense developed in life. This perspective
discusses the physical limits of chemoreception and gives an overview on the receptor
types developed during evolution to detect chemical signals from the outside world of
an organism. It discusses the interaction of chemoreceptors with downstream signaling
elements, especially the interaction between electrical and chemical signaling. It is further
considered how the primary chemosignal is appropriately amplified. Three examples of
chemosensory systems illustrate different strategies of such amplification.
Keywords: ionotropic receptor, metabotropic receptor, receptor kinase, GPCR, TRP channel
INTRODUCTION
Chemoreceptors transduce an external signal, a volatile molecule
(olfaction) or a molecule in solution (gustation) into an intracellular
signal. There are two major types of chemoreceptors,
ionotropic and metabotropic receptors. Ionotropic receptors
(IRs) are ion channels activated by ligand binding. The chemical
messenger elicits an immediate electrical signal in the sensory
cell. By contrast, activation of metabotropic receptor activates an
intracellular signaling cascade which may include enzyme activation,
second messenger production or activation of ion channels.
Receptor function and sensitivity are usually regulated by interaction
with accessory proteins. A high sensitivity of the chemoreceptive
machinery results from signal amplification which may
take place at various levels of signal processing.
While most chemoreceptors in mammals are metabotropic
receptors, chemoreception in insects is ionotropic. The authors
of a recent review thus asked whether the choice of a mechanism
for a sensory task is “chance or design” (Silbering and Benton,
2010), and concluded that the choice of ionotropic mechanisms
for insect chemoreception probably reflects a special mechanistic
advantage. For a detailed review on the evolution of insect
olfaction see (Hansson and Stensmyr, 2011).
PHYSICAL LIMITS OF CHEMOSENSATION
To detect low pheromone concentrations released in the order of
magnitude of ng per hour male insects have expanded the surface
area of their antennae (Hansson and Stensmyr, 2011). How are
receptor size and resolution related? Analysing bacterial chemotaxis
Berg and Purcell (1977) calculated the maximum precision
in sensing the concentration of a chemoattractant. The limit is
set by the noise due to Brownian motion when sensing a few
molecules. Escherichia coli can detect amino acids at nanomolar
concentration (Mao et al., 2003) which corresponds to only
a few molecules per cell volume. The fractional accuracy δc/c in
determining the concentration c is given by:
δc/c = 1/ Drcmt
where D is the diffusion coefficient of the chemoattractant, r the
receptor radius (e.g., cell radius), cm the mean concentration and
t the detection time (Berg and Purcell, 1977). This formula is
valid for a single receptor as well as for a receptor array such as
a cell surface equipped with receptors (Bialek and Setayeshgar,
2005). To determine a molecule with a diffusion coefficient of
10−5 cm2/s at a mean concentration of 1 μM with an accuracy
of 1%, a cell with a radius of 1 μm requires a measuring time
of 10 ms. For a single receptor with a radius of 1 nm a detection
time of 17 s would be required. Considering a fixed detection time
increasing the receptive surface indeed enhances the resolution as
in the above case of pheromone detection.
CHEMOSIGNAL PROCESSING AND AMPLIFICATION
External molecules bind to chemoreceptors located in the plasma
membrane, the subsequent receptor activation transduces the
external signal across the plasma membrane. For ligand-gated or
IRs, binding of the signal molecule opens an ion channel and
produces an electrical signal. This process is usually fast (micro
to milliseconds). The ion flux changes the membrane potential
and thus the electrical activity of the chemosensory neurons.
Signals transferred by excitatory IRs are amplified by depolarization
which activates various voltage-gated cation channels
leading to further depolarizion of OSNs. Another type of amplification
may take place when receptor activation leads to Ca2+
influx, either directly such as for the Ca2+-permeable TRP channels
or indirectly when the depolarization activates voltage-gated
Ca2+-channels. A rise in the free intracellular Ca2+ concentration
may activate various intracellular signaling cascades thereby
amplifying the chemical signal.
For metabotropic receptors binding of the signal molecule initiates
changes in intracellular chemical signaling such as enzyme
activation and production of second messengers. This process is
slower than ionotropic signaling and requires typically 50–150
milliseconds. However, for a tightly packed signaling cascade this
delay can be much shorter as in Drosophila photoreception where
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CELLULAR NEUROSCIENCE
Wicher Functional and evolutionary aspects of chemoreceptors
the receptor current activates 20 ms after photon absorption by
rhodopsin (Katz and Minke, 2009).
Since metabotropic signaling often involves G protein
activation, stimulation of enzymatic activity, and production of
second messengers, i.e., processes potentially contributing to a
signal amplification, this type of signaling may achieve a high
sensitivity of chemodetection. For example, in G protein-coupled
receptors (GPCRs) ligand binding activates a number of G proteins
setting a first level of signal amplification. This amplification
relies on a sufficient long dwelling time of the ligand to the receptor.
The residence time of the ligand which is inversely related to
the dissociation rate constant is thought to determine the effect
of receptor activation under in vivo conditions far from thermodynamic
equilibrium rather than the affinity defined as the
reciprocal of the equilibrium dissociation constant (Tummino
and Copeland, 2008). Another mechanism that may restrict the
number of activated G proteins is receptor desensitization (Kato
and Touhara, 2009). Furthermore, the signal amplification at G
protein level is controlled by proteins regulating their activity
cycle such as RGS proteins (regulators of G protein signaling),
AGS proteins (activators of G protein signaling) and GEFs (guanine
nucleotide exchange factors), for example in C. elegans
RGS proteins (Fukuto et al., 2004; Ferkey et al., 2007). G proteins
downstream activate enzymes such as adenylyl cyclases. The
cAMP production sets the second level of amplification since each
molecule may affect further downstream targets such as protein
kinases which might add another level of amplification.
Primary electrical signals can elicit secondary chemical signaling,
and vice versa, primary chemical signals can be transformed
into electrical signals as metabotropic receptors downstream
often target ion channels. For example, activation of the vanilloid
receptor VR1, a member of the TRP channel family, by
capsaicin induces a Ca2+ influx in the receptor cell. Ca2+ as a
universal intracellular signaling molecule can then activate Ca2+dependent
proteins such as cyclases and kinases. In mammalian
olfactory sensory neurons, odor binding activates the olfactory
receptor (OR), a GPCR bound to a stimulatory Golf protein which
in turn enhances the cAMP production via adenylyl cyclase stimulation.
cAMP binds to and opens cyclic nucleotide gated (CNG)
channels which depolarize the neuron and also conduct Ca2+.
Finally, Ca2+ activates Ca2+-dependent Cl− channels thereby
further depolarizing the cell (Kaupp, 2010). Similarly, receptor
guanylyl cyclases catalyze the production of cGMP which also
activate CNG channels to depolarize cells and enhance the free
Ca2+ concentration.
SPECIAL EXAMPLES FOR CHEMOSIGNAL AMPLIFICATION
BACTERIAL CHEMORECEPTORS
In Escherichia coli, chemoreceptors transmembrane methylaccepting
chemotaxis proteins (MCPs). They couple via a signal
conversion module to histidine autokinases CheA which are
inhibited upon chemoattractant and activated upon repellent
binding (Hazelbauer et al., 2008). The receptors for attractants
bind serine (Tsr), aspartate and maltose (Tar) ribose, glucose and
galactose (Trg), and dipeptides (Tap). The phosphorylation state
of CheA controls the flagellar motor. The chemoreceptors form
dimers which assemble to hexagonally packed trimers. These
arrays are concentrated in patches of about 250 nm diameter,
corresponding to 1% of the cell surface, and contain nearly half
the number of expressed chemoreceptors.
Within the signaling complex chemoreceptor/CheA there is a
signal amplification of ∼36, i.e., one receptor controls 36 kinase
molecules. Moreover, the receptors show strong cooperativity,
for attractant stimulation a Hill coefficient of 10 was observed
(Hazelbauer et al., 2008). Taken together, the lattice structure
of receptor arrangement allows a high degree of interaction
within the signaling complexes. This allows the bacteria to detect
nanomolar amino acid concentrations (Mao et al., 2003).
SEA URCHIN SPERM CELLS
The chemoattractant resact is released from the egg and binds
to a transmembrane receptor guanylyl cyclase on a sperm cell.
One ligand molecule gives rise to the production of ∼45 cGMP
molecules (Bönigk et al., 2009). One cGMP molecule is able to
activate CNGK, an atypical CNG channel with exclusive K+ permeability
that forms a pseudotetramer like voltage-gated Na+
or Ca2+ channels. Conventional CNG channels operate in the
micromolar concentration range and are activated in cooperative
manner, CNGK operates in the nanomolar range and is
activated by binding of a single molecule to the third repeat.
CNGK activation produces a transient hyperpolarization followed
by activation of voltage-gated Ca2+ channels allowing Ca2+
to enter the flagellum. At least 25 cGMP molecules were found
to be required for eliciting a Ca2+ signal. Thus, binding of one
chemoattractant molecule is sufficient to produce a number of
cGMP molecules that activate the highly cGMP-sensitive CNGK
channels which in turn elicit a behavioral response.
MAMMALIAN OLFACTORY RECEPTORS
Odor binding on mouse OR is extremely short. A dwelling time of
∼1 ms is not sufficient to activate on average one G protein, similar
as previously observed in frog ORs (Bhandawat et al., 2005;
Ben-Chaim et al., 2011). Thus, there is no signal amplification at
this level. Multiple binding of odor molecules to the same receptor
integrates odor signaling, and together with sufficient receptor
expression that multiplies binding events and thus the probability
of G protein activation leads to a stimulation of adenylyl
cyclase III. This raises the cAMP level to activate CNG channels
thereby depolarizing the cell and importing Ca2+. The signal
amplification takes place when Ca2+ activates Ca2+-dependent
Cl− channels which further depolarize the cell (Kaupp, 2010).
The delay between binding of odor molecules to the receptor
and the development of the receptor potential depends on
the odor concentration and can range between 100 ms at submicromolar
concentration and 25–40 ms at concentrations up to
100 μM (Ghatpande and Reisert, 2011). A delay in this order of
magnitude seems to be not limiting since a behavioral response
appears already 200 ms after odor stimulation (Abraham et al.,
2004).
CHEMORECEPTOR TYPES IN EVOLUTION
From bacteria to men both types of receptors, metabotropic and
ionotropic, are used to perceive chemical signals (Table 1) (Biswas
et al., 2009; Gees et al., 2010; Nordström et al., 2011). Most
of them are conserved during evolution, yet there are cases of
receptor gene degeneration such as the CO2-sensing guanylyl
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Wicher Functional and evolutionary aspects of chemoreceptors
Table 1 | Chemoreceptors in model organisms operating via a
metabotropic or an ionotropic mechanism.
Metabotropic Ionotropic
RC/RK GPCR GR/OR TRP IR
E. coli X − − − X
S. cerevisae − X − X −
C. elegans X X X X X
D. melanogaster − − X* X X
M. musculus X X − X −
RC/RK, receptor cyclase/receptor kinase; GPCR, G protein-coupled receptor;
GR/OR, gustatory receptor, olfactory receptor; TRP, ion channel family
named according to the first member to be discovered (“transient receptor
potential” channel in Drosophila photoreceptors); IR, “ionotropic receptor”,
a variant ionotropic glutamate receptor protein serving as olfactory receptor.
*GR/ORs in insects are 7-TM proteins as GPCRs, but are inversely
oriented in the membrane. They do not belong to the GPCR superfamily
according to a bioinformatics analysis (Benton et al., 2006; Nordström
et al., 2011), and form ionotropic receptors. X, receptor type reported for
that species.
cyclase D in primates (Young et al., 2007) or TRPC2, a channel
part of the pheromone signaling cascade, in men (Zufall,
2005).
Bacteria obtain nutrient information for chemotaxis from
receptor-associated kinases (Hazelbauer et al., 2008) and sense
amino acids using precursors of ionotropic glutamate receptors
(iGluRs, Chiu et al., 1999). Yeast express GPCRs to detect
sugar and pheromones (Versele et al., 2001) as well as TRP
channels for sensing aromatic compounds (Nilius and Owsianik,
2011). Highly sugar-sensitive receptors are the 12-TM proteins
Snf3/Rgt2 which regulate the expression of sugar transporters
(Gancedo, 2008).
In more complex organisms, specialized chemosensory neurons
detect volatile or external chemical messengers in solution.
Receptor activation induces a change in the electrical activity of
sensory neurons. IRs form ion channels gated by ligand binding
to the receptor. Metabotropic receptors couple to intracellular
signaling systems regulating the activity of targets such as ion
channels thereby changing the neuronal activity.
In nematodes metabotropic chemoreceptors comprise receptor
guanylyl cyclases and a large number of GPCRs (Bargmann,
2006). Receptors operating via an ionotropic mechanism are
TRP channels (Nilius and Owsianik, 2011), and “Ionotropic
Receptors” (IRs), ORs sensing general odors which are related to
iGluRs (Croset et al., 2010).
In insects, ORs are heterodimers composed of two proteins
with 7-transmembrane topology like GPCRs (Neuhaus et al.,
2005). However, there is no sequence similarity to other GPCRs
and the proteins are inversely oriented in the membrane (Benton
et al., 2006). One of these proteins is odor-specific, the other one a
co-receptor with chaperone function (Larsson et al., 2004). While
there are indications that odors initiate metabotropic signaling
(Wicher et al., 2008; Deng et al., 2011), the primary odor response
is ionotropic (Sato et al., 2008; Wicher et al., 2008). Other IRs
in insects are gustatory receptors [GRs, (Sato et al., 2011), IRs
(Benton et al., 2009), and TRP channels (Nilius and Owsianik,
2011)].
In mammals metabotropic chemoreceptors comprise receptor
tyrosine kinases (Petersen et al., 2011), guanylyl cyclases (Fülle
et al., 1995; Sun et al., 2009), and a large number of GPCRs
(Kaupp, 2010). Most olfactory and pheromone receptors are
GPCRs (Fleischer et al., 2009). Taste receptors for sweet, bitter,
and umami are GPCRs whereas those for sour and salty are
thought to be ionotropic (Chandrashekar et al., 2006). Receptors
for hot and spicy compounds as capsaicin, for cool compounds
as menthol or pungent compounds as mustard oil are also
ionotropic TRP channels (Damann et al., 2008). IRs are not
expressed in mammals (Croset et al., 2010). Instead, mammalian
central synapses express various subtypes of the related iGluRs.
CONCLUSION
Chemosensory systems are functional complexes of receptors and
downstream signaling elements. There seems to be no preference
for the use of either metabotropic or IRs for the detection of
chemicals during evolution. Moreover, receptors for a given sense
might be both metabotropic and ionotropic as seen above for
mammalian taste receptors. There is a pronounced conservation
of chemoreceptors during evolution. It is rather rare that receptors
disappear at a certain stage like the IRs in vertebrates. As seen
in mammalian ORs, there is no selection toward perfection. It is
possible to neglect the potential of G proteins for a signal amplification.
Although the chemosensory system was not optimized for
fast processing, the organism as a whole is capable of behaviorally
responding to odor stimulation in astonishingly short time. A
high sensitivity of chemosensory systems can be achieved by spatial
arrangements such as the chemosensory patches in bacteria
which provide the basis for high cooperativity of signaling elements.
On the other hand, the capability of sea urchin sperm cells
to react to single resact molecules demonstrates that high sensitivity
can also be obtained in a remarkably simple way unless the
internal signaling cascade allows a sufficiently high amplification
of the external signal.
ACKNOWLEDGMENTS
This study was supported by the Max Planck Society.
REFERENCES
Abraham, N. M., Spors, H., Carleton,
A., Margrie, T. W., Kuner, T., and
Schaefer, A. T. (2004). Maintaining
accuracy at the expense of speed:
stimulus similarity defines odor discrimination
time in mice. Neuron
44, 865–876.
Bargmann, C. I. (2006). Chemosensation
in C. elegans. WormBook.
doi: 10.1895/wormbook.1.123.1
Ben-Chaim, Y., Cheng, M. M., and Yau,
K. W. (2011). Unitary response of
mouse olfactory receptor neurons.
Proc. Natl. Acad. Sci. U.S.A. 108,
822–827.
Benton, R., Sachse, S., Michnick,
S. W., and Vosshall, L. B.
(2006). Atypical membrane
topology and heteromeric
function of Drosophila odorant
receptors in vivo. PLoS Biol.
4:e20. doi: 10.1371/journal.pbio.
0040020
Benton, R., Vannice, K. S., GomezDiaz,
C., and Vosshall, L. B. (2009).
Variant ionotropic glutamate receptors
as chemosensory receptors in
Drosophila. Cell 136, 149–162.
Berg, H. C., and Purcell, E. M. (1977).
Physics of chemoreception. Biophys.
J. 20, 193–219.
Frontiers in Cellular Neuroscience www.frontiersin.org October 2012 | Volume 6 | Article 48 | 3
Wicher Functional and evolutionary aspects of chemoreceptors
Bhandawat, V., Reisert, J., and Yau,
K. W. (2005). Elementary response
of olfactory receptor neurons to
odorants. Science 308, 1931–1934.
Bialek, W., and Setayeshgar, S. (2005).
Physical limits to biochemical signaling.
Proc. Natl. Acad. Sci. U.S.A.
102, 10040–10045.
Biswas, K. H., Shenoy, A. R., Dutta,
A., and Visweswariah, S. S. (2009).
The evolution of guanylyl cyclases
as multidomain proteins: conserved
features of kinase-cyclase domain
fusions. J. Mol. Evol. 68, 587–602.
Bönigk, W., Loogen, A., Seifert, R.,
Kashikar, N., Klemm, C., Krause,
E., et al. (2009). An atypical CNG
channel activated by a single cGMP
molecule controls sperm chemotaxis.
Sci. Signal 2, ra68.
Chandrashekar, J., Hoon, M. A., Ryba,
N. J., and Zuker, C. S. (2006). The
receptors and cells for mammalian
taste. Nature 444, 288–294.
Chiu, J., DeSalle, R., Lam, H. M.,
Meisel, L., and Coruzzi, G. (1999).
Molecular evolution of glutamate
receptors: a primitive signaling
mechanism that existed before
plants and animals diverged. Mol.
Biol. Evol. 16, 826–838.
Croset, V., Rytz, R., Cummins, S. F.,
Budd, A., Brawand, D., Kaessmann,
H., et al. (2010). Ancient protostome
origin of chemosensory
ionotropic glutamate receptors and
the evolution of insect taste and
olfaction. PLoS Genet. 6:e1001064.
doi: 10.1371/journal.pgen.1001064
Damann, N., Voets, T., and Nilius, B.
(2008). TRPs in our senses. Curr.
Biol. 18, R880–R889.
Deng, Y., Zhang, W., Farhat, K.,
Oberland, S., Gisselmann, G., and
Neuhaus, E. M. (2011). The stimulatory
Galpha(s) protein is involved
in olfactory signal transduction in
Drosophila. PLoS ONE 6:e18605.
doi: 10.1371/journal.pone.0018605
Ferkey, D. M., Hyde, R., Haspel, G.,
Dionne, H. M., Hess, H. A., Suzuki,
H., et al. (2007). C. elegans G protein
regulator RGS-3 controls sensitivity
to sensory stimuli. Neuron 53,
39–52.
Fleischer, J., Breer, H., and Strotmann,
J. (2009). Mammalian olfactory
receptors. Front. Cell. Neurosci. 3:9.
doi: 10.3389/neuro.03.009.2009
Fukuto, H. S., Ferkey, D. M., Apicella,
A. J., Lans, H., Sharmeen, T., Chen,
W., et al. (2004). G protein-coupled
receptor kinase function is essential
for chemosensation in C. elegans.
Neuron 42, 581–593.
Fülle, H. J., Vassar, R., Foster, D.
C., Yang, R. B., Axel, R., and
Garbers, D. L. (1995). A receptor
guanylyl cyclase expressed specifically
in olfactory sensory neurons.
Proc. Natl. Acad. Sci. U.S.A. 92,
3571–3575.
Gancedo, J. M. (2008). The early steps
of glucose signalling in yeast. FEMS
Microbiol. Rev. 32, 673–704.
Gees, M., Colsoul, B., and Nilius, B.
(2010). The role of transient receptor
potential cation channels in
Ca2+ signaling. Cold Spring Harb.
Perspect. Biol. 2, a003962.
Ghatpande, A. S., and Reisert,
J. (2011). Olfactory receptor
neuron responses coding for rapid
odour sampling. J. Physiol. 589,
2261–2273.
Hansson, B. S., and Stensmyr, M. C.
(2011). Evolution of insect olfaction.
Neuron 72, 698–711.
Hazelbauer, G. L., Falke, J. J., and
Parkinson, J. S. (2008). Bacterial
chemoreceptors: high-performance
signaling in networked arrays.
Trends Biochem. Sci. 33, 9–19.
Kato, A., and Touhara, K. (2009).
Mammalian olfactory receptors:
pharmacology, G protein coupling
and desensitization. Cell. Mol. Life
Sci. 66, 3743–3753.
Katz, B., and Minke, B. (2009).
Drosophila photoreceptors
and signaling mechanisms.
Front. Cell. Neurosci. 3:2. doi:
10.3389/neuro.03.002.2009
Kaupp, U. B. (2010). Olfactory signalling
in vertebrates and insects:
differences and commonalities. Nat.
Rev. Neurosci. 11, 188–200.
Larsson, M. C., Domingos, A. I., Jones,
W. D., Chiappe, M. E., Amrein, H.,
and Vosshall, L. B. (2004). Or83b
encodes a broadly expressed odorant
receptor essential for Drosophila
olfaction. Neuron 43, 703–714.
Mao, H., Cremer, P. S., and Manson,
M. D. (2003). A sensitive, versatile
microfluidic assay for bacterial
chemotaxis. Proc. Natl. Acad. Sci.
U.S.A. 100, 5449–5454.
Neuhaus, E. M., Gisselmann, G.,
Zhang, W., Dooley, R., Störtkuhl,
K., and Hatt, H. (2005). Odorant
receptor heterodimerization in
the olfactory system of Drosophila
melanogaster. Nat. Neurosci. 8,
15–17.
Nilius, B., and Owsianik, G. (2011). The
transient receptor potential family
of ion channels. Genome Biol. 12,
218.
Nordström, K. J., Almen, M. S.,
Edstam, M. M., Fredriksson, R., and
Schioth, H. B. (2011). Independent
HHsearch, Needleman-Wunschbased
and motif analyses reveals the
overall hierarchy for most of the G
protein-coupled receptor families.
Mol. Biol. Evol. 28, 2471–2480.
Petersen, C. I., Jheon, A. H.,
Mostowfi, P., Charles, C., Ching,
S., Thirumangalathu, S., et al.
(2011). FGF signaling regulates the
number of posterior taste papillae
by controlling progenitor field
size. PLoS Genet. 7:e1002098. doi:
10.1371/journal.pgen.1002098
Sato, K., Pellegrino, M., Nakagawa, T.,
Nakagawa, T., Vosshall, L. B., and
Touhara, K. (2008). Insect olfactory
receptors are heteromeric ligandgated
ion channels. Nature 452,
1002–1006.
Sato, K., Tanaka, K., and Touhara,
K. (2011). Sugar-regulated cation
channel formed by an insect gustatory
receptor. Proc. Natl. Acad. Sci.
U.S.A. 108, 11680–116805.
Silbering, A. F., and Benton, R. (2010).
Ionotropic and metabotropic mechanisms
in chemoreception: ‘chance
or design’? EMBO Rep. 11, 173–179.
Sun, L., Wang, H., Hu, J., Han, J.,
Matsunami, H., and Luo, M.
(2009). Guanylyl cyclase-D in
the olfactory CO2 neurons is
activated by bicarbonate. Proc.
Natl. Acad. Sci. U.S.A. 106,
2041–2046.
Tummino, P. J., and Copeland, R. A.
(2008). Residence time of receptorligand
complexes and its effect
on biological function. Biochemistry
47, 5481–5492.
Versele, M., Lemaire, K., and
Thevelein, J. M. (2001). Sex
and sugar in yeast: two distinct
GPCR systems. EMBO Rep. 2,
574–579.
Wicher, D., Schäfer, R., Bauernfeind,
R., Stensmyr, M. C., Heller,
R., Heinemann, S. H., et al.
(2008). Drosophila odorant receptors
are both ligand-gated and
cyclic-nucleotide-activated cation
channels. Nature 452, 1007–1011.
Young, J. M., Waters, H., Dong, C.,
Fulle, H. J., and Liman, E. R.
(2007). Degeneration of the olfactory
guanylyl cyclase D gene during
primate evolution. PLoS ONE
2:e884. doi: 10.1371/journal.pone.
0000884
Zufall, F. (2005). The TRPC2 ion channel
and pheromone sensing in the
accessory olfactory system. Naunyn
Schmiedebergs Arch. Pharmacol.
371, 245–250.
Conflict of Interest Statement: The
author declares that the research
was conducted in the absence of any
commercial or financial relationships
that could be construed as a potential
conflict of interest.
Received: 31 July 2012; accepted: 08
October 2012; published online: 26
October 2012.
Citation: Wicher D (2012) Functional
and evolutionary aspects of chemoreceptors.
Front. Cell. Neurosci. 6:48. doi:
10.3389/fncel.2012.00048
Copyright © 2012 Wicher. This is
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