Assignment of olfactory receptor RNA to neurons

A gene for the receptor of a given odorant is expressed
in an individual in only a few neurons.
Ngai et al. 1993 classified individual olfactory
neurons in the olfactory epithelium of the catfish
(Ictalurus punctatus). Only 0.5–2% of all olfactory
neurons recognize a given receptor
probe such as probe 202 (1) or 32 (2). Odors are
distinguished in the brain according to which
neurons are stimulated. The topographical
position of each neuron is specific for each
odorant.

Subfamilies within the multigene family

Amino acid sequences derived from partial nucleotide
sequences of cDNA clones (F2–F24) (1)
investigated by Buck and Axel (1991) were very
variable, especially in transmembrane domains
III and IV. Within subfamilies, there was homology
due to conserved sequences (2). For example,
F12 and F13 differ in only 4 of 44 positions
(91% identical).

Mammalian Taste Receptor Gene Family

Aside from the main olfactory system, mammals
have evolved two other chemosensory
systems, the taste receptor gene family (for bitter
taste) and the mammalian pheromone receptor
gene family. Five different types of taste
can be perceived: salty, sour, bitter, sweet, and
umani (the taste of monosodium glutamate,
present in Asian food). Salty and sour tastes involve
direct effects due to the entry of H+ and
Na+ ions through specialized membrane channels.
In contrast, bitter, sweet, and umani tastes
are mediated via a G protein-coupled receptor
(GPCR) signaling pathway system. A sweet taste
may herald a desirable carbohydrate content,
whereas a bitter taste is associated with potentially
toxic substances such as alkaloids, cyanides,
or other detrimental aromatic compounds.

Mammalian chemosensory epithelia

The oral and nasal cavities of mammals contain
three distinct chemosensory epithelia: (i) the
main olfactory epithelium (MOE) containing
sensory cells with odorant receptors in the nose
(see previous page), (ii) the taste sensory
epithelium of the taste buds of the tongue, soft
palate, and epiglottis, and (iii) the vomeronasal
organ (VOM, also called Jacobson’s organ), a
tubular structure in the nasal septum containing
sensory cells with pheromone receptors.
The main olfactory bulb (MOB) relays signals
from the MOE to the olfactory cortex of the
brain. The accessory olfactory bulb (AOB) relays
signals from the VOM to areas of the amygdala
and hypothalamus.

Mammalian chemosensory system

The receptor cells are organized in three corresponding
molecular and cellular chemosensory
systems. Each neuron of the main olfactory
sensory system (1) expresses one of the different
olfactory receptor genes and sends axons to
specific glomeruli of the main olfactory bulb
(mitral cells). The odorant receptor (OR) gene
family comprises about 1000 members, each
encoding a seven-transmembrane cyclic nucleotide-
gated channel with distinct odorant
specificity (G-olfactory proteins, Golf). The bitter
taste sensory system (2) connects axonal projections
of receptor cells in the taste sensory
epithelium of the taste buds to gustatory nuclei
of the brain stem. Two families of taste receptors,
the TIRs (two genes) and T2Rs (50–80
genes of the gustducin class) have been described.
Two families of mammalian putative
pheromone receptors (V1Rs and V2Rs) are encoded
by 30–50 and over 100 genes, respectively
(3).

Taste receptor gene family

The two novel taste receptor gene families,
T1R1 and T1R2, are expressed in distinct subsets
of taste receptor cells. The figure shows an
alignment of the predicted amino acid
sequences of 23 different T2 receptors (T2Rs) of
human (h), rat (r), and mouse (m) origin between
the first (TM1) and the third (TM3) transmembrane
domain. Dark blue indicates identity
in at least half of the aligned sequences;
light blue represents conserved substitutions;
and the remainder are divergent regions. They
reflect the ability to bind many structurally
different ligands. The T2R genes cluster on a few
chromosomes, human chromosomes 5, 7, and
12 and mouse chromosomes 6 and 15.

Expression of many taste receptor genes in the same cell

Unlike olfactory system receptor cells, individual
taste receptor cells express multiple
T2R receptors. Up to ten T2R probes hybridize to
only a few cells, shown darkened (1). Doublelabel
fluorescent in-situ hybridization shows
that different receptor genes (2, T2R-3 in green
and T2R-7 in red, 3) are expressed in the same
taste receptor cell. The T2Rs confer high sensitivity
for bitter substances at low concentrations
but do not distinguish between them.