Taste transduction and channel synapses in taste buds

Abstract

The variety of taste sensations, including sweet, umami, bitter, sour, and salty, arises from diverse taste cells, each of which expresses specific taste sensor molecules and associated components for downstream signal transduction cascades. Recent years have witnessed major advances in our understanding of the molecular mechanisms underlying transduction of basic tastes in taste buds, including the identification of the bona fide sour sensor H⁺ channel OTOP1, and elucidation of transduction of the amiloride-sensitive component of salty taste (the taste of sodium) and the TAS1R-independent component of sweet taste (the taste of sugar). Studies have also discovered an unconventional chemical synapse termed "channel synapse" which employs an action potential-activated CALHM1/3 ion channel instead of exocytosis of synaptic vesicles as the conduit for neurotransmitter release that links taste cells to afferent neurons. New images of the channel synapse and determinations of the structures of CALHM channels have provided structural and functional insights into this unique synapse. In this review, we discuss the current view of taste transduction and neurotransmission with emphasis on recent advances in the field.

Keywords: CALHM; Ion channel; Sensory; Synapse; Taste.

Fig. 1

Signal transduction and neurotransmission of tastes. a Taste coding in taste buds. Each taste quality is generally sensed by dedicated taste cells: sweet, bitter, umami, sour, and sodium cells. Whereas sour taste cells are designated as type III cells, sweet, bitter, and umami taste cells are considered together as type II cells because they share a common signaling cascade. Note that high-salt taste relies on bitter and sour cells. b Sour transduction in type III cells involves OTOP1 and K_ir2.1 as the H⁺ sensor and signal amplifier channels, respectively, and employs conventional vesicular synapses for neurotransmission. c Among type II cells, sweet, umami, and bitter cells differ in the types of taste receptors but share a similar signaling pathway, where the activation of TRPM5 channels generates a depolarization to trigger action potential firing. Sodium taste transduction is initiated by Na⁺ influx through ENaC, which induces a supra-threshold depolarization for action potential generation. Both type II cells and sodium taste cells employ the channel synapse involving CALHM1/3 channels as the conduit for action potential-dependent neurotransmitter release. OTOP1, Otopetrin1; K_ir2.1, inward rectifier K⁺ channel; ΔpH, intracellular acidification; PLCβ2, phospholipase Cβ2; IP₃, inositol trisphosphate; DAG, diacylglycerol; ER, endoplasmic reticulum; IP₃R3, inositol trisphosphate receptor type 3; TRPM, transient receptor potential melastatin; CALHM, calcium homeostasis modulator; ENaC, epithelial Na⁺ channel

Fig. 2

Structure of the channel synapse defined by characteristic localization of CALHM channels, afferent nerve fibers, and mitochondria. a Super-resolution image of a sodium taste cell identified by expression of GCaMP3 (green) with co-staining of CALHM1 (red) and an afferent nerve fiber (P2X2, blue) in a fungiform taste bud of an ENaCα-GCaMP3 mouse. Data were taken from [60]. b Super-resolution image of a type II taste cell identified by expression of PLCβ2 (blue) with co-staining of CALHM1 (red) and mitochondria (cytochrome c, green) in a circumvallate taste bud of a B6 mouse. Arrowheads indicate channel synapses where mitochondria, CALHM1, and afferent nerves localize closely together. Scale bars, 2 μm

Fig. 3

Structure of the CALHM1 channel. a Overall structure of the killifish CALHM1 octamer (PDB ID: 6LMT), viewed from the extracellular side (left) and parallel to the membrane (right). b Channel pore of killifish CALHM1, shown in cross section of the surface representation. Each region for two opposing subunits is colored as follows: NTH, pink; TM1, purple; TM2, blue; TM3, light green; TM4, orange; extracellular region, yellow; parts of TM2 and TM3 at the intracellular side, cyan; and CTH, red