Page 36 - Science

INSIGHTS | PERSPECTIVES

taste receptor, behavioral analysis is needed quired for otoconia formation, in support and enhance pain by increasing the ac-
to be certain. Complicating the behavioral cells. However, the relationship of OTOP1 tivities of channels in nociceptors, such as
analyses is that high acid concentrations and these vesicles to otoconia formation is TRPV1 (transient receptor potential cation
not only stimulate TRCs but also activate unclear. Ca -channel activity can be inhib- channel subfamily V member 1), in pe-
2+
nociceptor (pain) afferents (8). Thus, in the ited by intracellular acidification. Therefore, ripheral sensory neurons. Because positive
absence of a repulsion to high sour taste, OTOP1 might contribute to a homeostatic allosteric modulation of TRPV1 by mild
such as in the tilted mice, H + would still mechanism to maintain pH. Opposite to acidification only occurs in response to ex-
+
cause aversive behavior because it would functioning in H influx, as in TRCs, it might tracellular acidification, OTOP-dependent
+
activate nociceptive neurons through an promote H efflux from support cells, to pre- H + influx might attenuate nociception.
OTOP1-independent mechanism. vent intracellular acidification. Indeed, OTOP1 expression is increased in
Because low levels of sour are appeal- OTOPs comprise a conserved protein dorsal root ganglion (DRG) neurons ex-
ing, and high levels are aversive, do sep- family, and Tu et al. found that mouse posed to neuropathic conditions (14). How-
+
arate TRCs and H + channels respond to OTOP1 and OTOP2, human OTOP1, and a ever, H influx would have to be moderate
slightly and strongly acidic foods? This fly Otop each conduct H + upon lowering to prevent cytotoxic acidosis.
would be reminiscent of Na -responsive extracellular pH. OTOP family members Given their wide expression patterns,
+
TRCs, whereby one type senses low Na are expressed in many cell types in humans loss of OTOPs might result in many pa-
+
concentrations through the ENaC channel and mice. Although intracellular acidifica- thologies. The intracellular pH of most
and stimulates feeding and another class tion is typically cytotoxic, there are cells cells is ~7.2, and the extracellular pH is
senses high Na concentrations and other other than type III TRCs that may be usually ~7.4. However, cancer cells often
+
+
salts through an unknown channel and in- endowed with H -influx channels. For ex- have an increased intracellular pH (~7.4),
duces repulsion (4, 9). Alternatively, there ample, osteoclasts, which are exposed to whereas the extracellular pH is reduced
may exist only one class of H -activated low extracellular pH (<5.5) in resorption (6.8 to 7.0) (15). This pH dysregulation can
+
TRC. Slight tanginess would stimulate pits in bones, have a H -influx pathway contribute to cancer by attenuating apop-
+
the TRCs slightly and promote feeding, (13). However, it is only slightly inhibited tosis and promoting cell proliferation and Downloaded from
whereas high acidity could induce a greater by Zn 2+ (13), differing from OTOP-depen- directed cell migration (15). Might loss of
response of the same TRCs and cause re- dent conductances. OTOPs contribute to certain cancers by
+
pulsion. Type III TRCs are also required A decrease in extracellular pH can ac- limiting H influx, which would otherwise
for sensing water and carbonation and company tissue injury or inflammation reduce intracellular pH? Mouse OTOP2
contribute to detecting high and OTOP3 have somewhat
salt concentrations (9–11). Are distinct biophysical properties
these the same, overlapping, or Sour taste reception from OTOP1 (2). How does this
distinct PKD2L1-positive type Mice and humans have five basic tastes: sweet, bitter, salty, umami, and sour. relate to their biological roles? http://science.sciencemag.org/
III TRCs that express OTOP1? Many receptors and ion channels in taste buds are critical for detecting these Do different OTOPs interact
Does loss of OTOP1 affect any chemicals in foods, but the sour taste receptor has been elusive. The H -selective with distinct downstream ef-
+
of these other tastes? Interest- channel OTOP1 is expressed in, and functions in, mouse acid-sensing taste fector proteins, which expand
ingly, acidification suppresses receptor cells in taste buds of the tongue, and may be essential for sour taste. their functions? Clearly, there
the water taste response (10). is much more to learn about
+
The finding that OTOP1 is a H Taste bud this pHamily. j
channel raises questions about Mouse Tongue Taste
its role in the vestibular system. receptor cell REFERENCES on March 1, 2018
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(2006).
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+
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(2016).
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2+
to regulate intracellular Ca e0123342 (2015).
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be required to attain high Ca Cytoplasm of sour-sensing H + OTOP1
2+
concentrations in globular sub- taste receptor cell channel
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992 2 MARCH 2018 • VOL 359 ISSUE 6379 sciencemag.org SCIENCE
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