Functional expression of TMEM16A in taste bud cells

Guarascio, Domenico M; Gonzalez-Velandia, Kevin Y.; Hernandez-Clavijo, Andres; Menini, Anna; Pifferi, Simone

doi:10.1113/jp281645

Cited by 10 publications

(6 citation statements)

References 83 publications

(218 reference statements)

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“…In addition to our proposed synaptic model, ATP-evoked Ca 21 mobilization in Type I cells activates Ca-dependent Clchannels in the apical tips of Type I cells and thus may participate in spatial buffering of ions to permit repetitive firing of chemosensory taste cells (Dvoryanchikov et al, 2009;Cherkashin et al, 2016;Guarascio et al, 2021).…”

Section: Discussionmentioning

confidence: 97%

“…These cells express the ectonucleotidase, NTPase2, that breaks down ATP released by Type II cells during taste excitation (Bartel et al, 2006;Vandenbeuch et al, 2013). Type I taste bud cells have also been proposed to help regulate the ionic environment in taste buds, in particular the concentrations of K 1 and Cl - (Dvoryanchikov et al, 2009;Cherkashin et al, 2016;Guarascio et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

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“Tripartite Synapses” in Taste Buds: A Role for Type I Glial-like Taste Cells

et al. 2021

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In mammalian taste buds, Type I cells comprise half of all cells. These are termed “glial-like” based on morphologic and molecular features, but there are limited studies describing their function. We tested whether Type I cells sense chemosensory activation of adjacent chemosensory (i.e., Types II and III) taste bud cells, similar to synaptic glia. UsingGad2;;GCaMP3 mice of both sexes, we confirmed by immunostaining that, within taste buds, GCaMP expression is predominantly in Type I cells (with no Type II and ≈28% Type III cells expressing weakly). In dissociated taste buds, GCaMP+ Type I cells responded to bath-applied ATP (10-100 μm) but not to 5-HT (transmitters released by Type II or III cells, respectively). Type I cells also did not respond to taste stimuli (5 μmcycloheximide, 1 mmdenatonium). In lingual slice preparations also, Type I cells responded to bath-applied ATP (10-100 μm). However, when taste buds in the slice were stimulated with bitter tastants (cycloheximide, denatonium, quinine), Type I cells responded robustly. Taste-evoked responses of Type I cells in the slice preparation were significantly reduced by desensitizing purinoceptors or by purinoceptor antagonists (suramin, PPADS), and were essentially eliminated by blocking synaptic ATP release (carbenoxolone) or degrading extracellular ATP (apyrase). Thus, taste-evoked release of afferent ATP from type II chemosensory cells, in addition to exciting gustatory afferent fibers, also activates glial-like Type I taste cells. We speculate that Type I cells sense chemosensory activation and that they participate in synaptic signaling, similarly to glial cells at CNS tripartite synapses.SIGNIFICANCE STATEMENTMost studies of taste buds view the chemosensitive excitable cells that express taste receptors as the sole mediators of taste detection and transmission to the CNS. Type I “glial-like” cells, with their ensheathing morphology, are mostly viewed as responsible for clearing neurotransmitters and as the “glue” holding the taste bud together. In the present study, we demonstrate that, when intact taste buds respond to their natural stimuli, Type I cells sense the activation of the chemosensory cells by detecting the afferent transmitter. Because Type I cells synthesize GABA, a known gliotransmitter, and cognate receptors are present on both presynaptic and postsynaptic elements, Type I cells may participate in GABAergic synaptic transmission in the manner of astrocytes at tripartite synapses.

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Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

“Tripartite Synapses” in Taste Buds: A Role for Type I Glial-like Taste Cells

et al. 2021

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“…In negative control experiments, only the primary antibody step was omitted, and no fluorescence signal was detected, supporting the specificity of antibody. The specificity of TMEM16A antibody (Guarascio et al., 2021) and COX‐2 antibody (Nilsson et al., 2012) used in the present study has been validated using TMEM16A knockout mice and COX‐2 knockout mice, respectively.…”

Section: Methodsmentioning

confidence: 89%

Roles of endothelial prostaglandin I₂ in maintaining synchronous spontaneous Ca²⁺ transients in rectal capillary pericytes

Mitsui,

Miwa‐Nishimura,

Hashitani

2023

The Journal of Physiology

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In hollow visceral organs, capillary pericytes appear to drive spontaneous Ca2+ transients in the upstream arterioles. Here, mechanisms underlying the intercellular synchrony of pericyte Ca2+ transients were explored. Ca2+ dynamics in NG2 chondroitin sulphate proteoglycan (NG2)‐expressing capillary pericytes were examined using rectal mucosa–submucosa preparations of NG2‐GCaMP6 mice. Spontaneous Ca2+ transients arising from endoplasmic reticulum Ca2+ release were synchronously developed amongst capillary pericytes in a gap junction blocker (3 μM carbenoxolone)‐sensitive manner and could spread into upstream vascular segments. Spontaneous Ca2+ transients were suppressed by the Ca2+‐activated Cl− channel (CaCC) blocker niflumic acid and their synchrony was diminished by a TMEM16A inhibitor (3 μM Ani9) in accordance with TMEM16A immunoreactivity in pericytes. In capillaries where cyclooxygenase (COX)‐2 immunoreactivity was expressed in endothelium but not pericytes, non‐selective COX inhibitors (1 μM indomethacin or 10 μM diclofenac) or COX‐2 inhibitor (10 μM NS 398) disrupted the synchrony of spontaneous Ca2+ transients and raised the basal Ca2+ level. Subsequent prostaglandin I2 (PGI2; 100 nM) or the KATP channel opener levcromakalim restored the synchrony with a reduction in the Ca2+ level. PGI2 receptor antagonist (1 μM RO1138452) also disrupted the synchrony of spontaneous Ca2+ transients and increased the basal Ca2+ level. Subsequent levcromakalim restored the synchrony and reversed the Ca2+ rise. Thus, the synchrony of spontaneous Ca2+ transients in pericytes appears to be developed by the spread of spontaneous transient depolarisations arising from the opening of TMEM16A CaCCs. Endothelial PGI2 may play a role in maintaining the synchrony, presumably by stabilising the resting membrane potential in pericytes. imageKey points Capillary pericytes in the rectal mucosa generate synchronous spontaneous Ca2+ transients that could spread into the upstream vascular segment. Spontaneous Ca2+ release from the endoplasmic reticulum (ER) triggers the opening of Ca2+‐activated Cl− channel TMEM16A and resultant depolarisations that spread amongst pericytes via gap junctions, establishing the synchrony of spontaneous Ca2+ transients in pericytes. Prostaglandin I2 (PGI2), which is constitutively produced by the endothelium depending on cyclooxygenase‐2, appears to prevent premature ER Ca2+ releases in the pericytes allowing periodic, regenerative Ca2+ releases. Endothelial PGI2 may maintain the synchrony of pericyte activity by stabilising pericyte resting membrane potential by opening of KATP channels.

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“…Adenosine triphosphate (ATP) is an important extracellular signalling molecule in several epithelia, and serves as a neurotransmitter in both the peripheral and central nervous systems. Extracellular ATP binds to purinergic P2Y (G q -protein-coupled receptors) and P2X (non-selective cation channels) receptors, leading to an increase in [Ca 2+ ] i that may promote activation of TMEM16x scramblases [209] and/or TMEM16x channels in airway epithelial cells [210][211][212][213][214], colonic epithelial cells [215], murine taste cells [216], supporting cells of the murine olfactory epithelium [217], and arterial smooth muscle cells [180].…”

Section: Intra-and Extracellular Atpmentioning

confidence: 99%

Polymodal Control of TMEM16x Channels and Scramblases

Agostinelli

Tammaro

2022

IJMS

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The TMEM16A/anoctamin-1 calcium-activated chloride channel (CaCC) contributes to a range of vital functions, such as the control of vascular tone and epithelial ion transport. The channel is a founding member of a family of 10 proteins (TMEM16x) with varied functions; some members (i.e., TMEM16A and TMEM16B) serve as CaCCs, while others are lipid scramblases, combine channel and scramblase function, or perform additional cellular roles. TMEM16x proteins are typically activated by agonist-induced Ca2+ release evoked by Gq-protein-coupled receptor (GqPCR) activation; thus, TMEM16x proteins link Ca2+-signalling with cell electrical activity and/or lipid transport. Recent studies demonstrate that a range of other cellular factors—including plasmalemmal lipids, pH, hypoxia, ATP and auxiliary proteins—also control the activity of the TMEM16A channel and its paralogues, suggesting that the TMEM16x proteins are effectively polymodal sensors of cellular homeostasis. Here, we review the molecular pathophysiology, structural biology, and mechanisms of regulation of TMEM16x proteins by multiple cellular factors.

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Functional expression of TMEM16A in taste bud cells

Cited by 10 publications

References 83 publications

“Tripartite Synapses” in Taste Buds: A Role for Type I Glial-like Taste Cells

“Tripartite Synapses” in Taste Buds: A Role for Type I Glial-like Taste Cells

Roles of endothelial prostaglandin I₂ in maintaining synchronous spontaneous Ca²⁺ transients in rectal capillary pericytes

Polymodal Control of TMEM16x Channels and Scramblases

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Functional expression of TMEM16A in taste bud cells

Cited by 10 publications

References 83 publications

“Tripartite Synapses” in Taste Buds: A Role for Type I Glial-like Taste Cells

“Tripartite Synapses” in Taste Buds: A Role for Type I Glial-like Taste Cells

Roles of endothelial prostaglandin I2 in maintaining synchronous spontaneous Ca2+ transients in rectal capillary pericytes

Polymodal Control of TMEM16x Channels and Scramblases

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Roles of endothelial prostaglandin I₂ in maintaining synchronous spontaneous Ca²⁺ transients in rectal capillary pericytes