Loss of Otopetrin 1 affects thermoregulation during fasting in mice.

Objective: Otopetrin 1 (OTOP1) is a proton channel that is highly expressed in brown adipose tissue. We examined the physiology of Otop1-/- mice, which lack functional OTOP1.

Methods: Mice were studied by indirect calorimetry and telemetric ambulatory body temperature monitoring.

Structural motifs for subtype-specific pH-sensitive gating of vertebrate otopetrin proton channels.

Otopetrin (OTOP) channels are proton-selective ion channels conserved among vertebrates and invertebrates, with no structural similarity to other ion channels. There are three vertebrate OTOP channels (OTOP1, OTOP2, and OTOP3), of which one (OTOP1) functions as a sour taste receptor. Whether extracellular protons gate OTOP channels, in addition to permeating them, was not known.

Cellular and Neural Responses to Sour Stimuli Require the Proton Channel Otop1.

The sense of taste allows animals to sample chemicals in the environment prior to ingestion. Of the five basic tastes, sour, the taste of acids, had remained among the most mysterious. Acids are detected by type III taste receptor cells (TRCs), located in taste buds across the tongue and palate epithelium.

Structures of the otopetrin proton channels Otop1 and Otop3.

Otopetrins (Otop1-Otop3) comprise one of two known eukaryotic proton-selective channel families. Otop1 is required for otoconia formation and a candidate mammalian sour taste receptor. Here we report cryo-EM structures of zebrafish Otop1 and chicken Otop3 in lipid nanodiscs.

Activation Stoichiometry and Pore Architecture of TRPA1 Probed with Channel Concatemers.

The nociceptor ion channel TRPA1 detects a wide range of hazardous chemicals, including reactive electrophiles such as cinnamaldehyde, which gate the channel allowing Na and Ca entry. TRPA1 assembles as a tetramer, with a central pore within which an aspartate residue (D918) determines Ca permeability. Here, we report that introduction of histidine at this position, D918H, makes TRPA1 channels sensitive to block by nanomolar concentration of Zn and can be used to functionally tag subunits in concatemers.

An evolutionarily conserved gene family encodes proton-selective ion channels.

Ion channels form the basis for cellular electrical signaling. Despite the scores of genetically identified ion channels selective for other monatomic ions, only one type of proton-selective ion channel has been found in eukaryotic cells. By comparative transcriptome analysis of mouse taste receptor cells, we identified Otopetrin1 (OTOP1), a protein required for development of gravity-sensing otoconia in the vestibular system, as forming a proton-selective ion channel.

The K+ channel KIR2.1 functions in tandem with proton influx to mediate sour taste transduction.

Sour taste is detected by a subset of taste cells on the tongue and palate epithelium that respond to acids with trains of action potentials. Entry of protons through a Zn(2+)-sensitive proton conductance that is specific to sour taste cells has been shown to be the initial event in sour taste transduction. Whether this conductance acts in concert with other channels sensitive to changes in intracellular pH, however, is not known.