Abstracts - Association for Chemoreception Sciences

#1 GIVAUDAN LECTURE
Normal and Cancer Stem Cells and the
Development of Malignancy
Robert A. Weinberg
Member, Whitehead Institute and Director, MIT Ludwig Center
for Cancer Research
The progression of carcinoma cells in primary tumors to a state of
high-grade malignancy involves the acquisition of a variety of cell
traits, including motility, invasiveness, and an increased resistance
to apoptosis. These traits are all components of a complex cellbiological
program termed the epithelial-mesenchymal transition
(EMT), which normally plays a role in various steps of embryonic
morphogenesis and in wound healing. By resurrecting this multifaceted
program, cancer cells are able to gain access in a single step
to these multiple traits, which in turn empowers them to invade
and disseminate. Indeed, the invasive edges of carcinomas often
exhibit cells that exhibit signs of having activated an EMT
program. Recently it has become apparent that the EMT, rather
than creating bona fide mesenchymal cells, actually creates
epithelial stem cells that exhibit many mesenchymal traits.
Accordingly, the EMT program represents the key to enable the
conversion of more differentiated epithelial cells into epithelial
stem cells, which holds implications for both normal epithelial
cells biology and cancer pathogenesis.
#2 PLATFORM PRESENTATIONS -
TIP OF THE TONGUE
Analysis of Drosophila TRPA1 reveals an ancient origin for
human chemical nociception
Paul A Garrity 1 , Kyeongjin Kang 1 , Stefan R Pulver 1, 2 ,
Vincent C Panzano 1 , Leslie C Griffith 1 , Douglas L Theobald 1
1
Brandeis University Waltham, MA, USA, 2 University of
Cambridge Cambridge, United Kingdom
Chemical nociception, the detection of tissue-damaging chemicals,
is important for animal survival and causes human pain and
inflammation, but its evolutionary origins are largely unknown.
Reactive electrophiles are a class of noxious compounds humans
find pungent and irritating, like allyl isothiocyanate (in wasabi)
and acrolein (in cigarette smoke). Insects to humans find reactive
electrophiles aversive, but whether this reflects conservation of an
ancient sensory modality has been unclear. Using a combination
of genetics and physiology, we have determined the molecular
basis of reactive electrophile detection in flies. We find that
dTRPA1, the Drosophila melanogaster ortholog of the human
irritant sensor, acts in gustatory chemosensors to inhibit reactive
electrophile ingestion. Both fly and mosquito TRPA1 orthologs
act as molecular sensors of electrophiles, and they respond to
these chemical via a mechanism conserved with vertebrate
TRPA1s. Phylogenetic analyses indicate invertebrate and
vertebrate TRPA1s share a common ancestor that possessed
critical characteristics required for electrophile detection. These
findings support emergence of TRPA1-based electrophile
detection in a common bilaterian ancestor, with widespread
conservation throughout vertebrate and invertebrate evolution.
Such conservation contrasts with the evolutionary divergence of
canonical olfactory and gustatory receptors and may relate to
electrophile toxicity. These findings suggest that human
perceptions of reactive electrophiles rely on an ancient chemical
sensor conserved across ~500 million years of animal evolution.
Acknowledgements: NIMH (R21 MH080206, P.A.G., RO1
MH067284 , L.C.G.) and NINDS (PO1 NS044232)
Abstracts are printed as submitted by the author(s)
#3 PLATFORM PRESENTATIONS -
TIP OF THE TONGUE
A subpopulation of mouse Type II taste cells express functional
voltage-gated calcium channels
Pin Liu, Timothy A. Gilbertson
Department of Biology and The Center for Advanced Nutrition,
Utah State University Logan, UT, USA
Type II taste cells contain receptors and signaling components for
sweet, bitter, and umami tastants, and are responsible for
transducing complex taste stimuli via the phospholipase C (PLC)
pathway. Type II cells communicate with the afferent nerve or
Type III cells via non-vesicular purinergic signaling. Previous
studies concluded that Type II cells lack voltage-gated Ca 2+
channels (VGCCs), while Type III cells express the VGCCs
required for synaptic transmission. However, our functional
calcium imaging data in C57Bl/6 mice showed that a small but
significant subpopulation of Type II cells, identified by their
responses to an established tastant mixture, also responded to high
KCl, consistent with the expression of VGCCs in these cells. To
explore whether VGCCs are expressed in subpopulations of type
II cells, transgenic mice expressing enhanced green fluorescent
protein (GFP) under control of the PLCß2 promoter (PLCß2-
GFP) were used in both functional calcium imaging and patch
clamp recording. Calcium imaging data showed that high KCl
elicited a robust intracellular calcium rise in over half of PLCß2-
GFP taste cells, consistent with the expression of VGCCs. Patch
clamp recording showed that VGCC currents were present in 8
out of 33 PLCß2-GFP taste cells. The VGCC current was large
(200~500 pA) when the whole cell configuration was first
established, but washed out quickly (t = 138 s). This rapid
washout may partially explain why VGCC current has been
rarely seen in type II cells electrophysiologically. Our findings
strongly suggest that functional VGCCs are expressed in
subpopulations of Type II cells and question the current model of
cell signaling within the taste bud as well as the utility of high KCl
to identify unequivocally type III cells within the taste bud.
Acknowledgements: Supported by NIH DK059611 and
International Flavors & Fragrances.
#4 PLATFORM PRESENTATIONS -
TIP OF THE TONGUE
Ryanodine Receptors selectively contribute to the formation
of Taste evoked-calcium signals in Mouse taste cells
Michelle R Rebello, Kathryn F Medler
State University of New York at Buffalo Buffalo, NY, USA
While it has been well established that different taste stimuli
activate distinct signaling pathways in taste receptor cells, the
signal transduction mechanisms associated with these pathways
have not been completely characterized. Bitter, umami and sweet
taste stimuli activate G-protein coupled receptors (GPCRs) to
cause Ca 2+ release from intracellular stores, which is known to
occur in Type II cells via a PLCb2/IP3R3 signaling pathway. Sour
stimuli depolarize taste cells to cause Ca 2+ influx through voltagegated
calcium channels (VGCCs), presumably in taste cells with
chemical synapses. The transduction pathways of salty stimuli are
less well defined. There is also a sub-population of taste cells that
express VGCCs and detect bitter taste stimuli but do not express
the PLCb2/IP3R3 pathway. These cells are termed dualresponsive
and appear to express PLCb3 and IP3R1. While it is
recognized that bitter, sweet and umami taste stimuli activate
GPCRs to evoke IP3-mediated Ca 2+ release from internal stores,
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