The otopetrin family is a group of

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

s that were first identified based on their essential role in the

vestibular system The vestibular system, in vertebrates, is a sensory system that creates the sense of balance and spatial orientation for the purpose of coordinating motor coordination, movement with balance. Together with the cochlea, a part of the auditory sys ...

, and were later shown to form proton-selective

ion channel Ion channels are pore-forming membrane proteins that allow ions to pass through the channel pore. Their functions include establishing a resting membrane potential, shaping action potentials and other electrical signals by Gating (electrophysiol ...

s expressed in many different tissues, including

taste The gustatory system or sense of taste is the sensory system that is partially responsible for the perception of taste. Taste is the perception stimulated when a substance in the mouth biochemistry, reacts chemically with taste receptor cells l ...

receptor cells. They are named after the Greek word "o̱tós," which means ear and "pétrā," which means rock, in reference to their role in the formation of

otoconia An otolith (, ' ear + , ', a stone), also called otoconium, statolith, or statoconium, is a calcium carbonate structure in the saccule or utricle of the inner ear, specifically in the vestibular system of vertebrates. The saccule and utricle, ...

otoliths An otolith (, ' ear + , ', a stone), also called otoconium, statolith, or statoconium, is a calcium carbonate structure in the saccule or utricle of the inner ear, specifically in the vestibular system of vertebrates. The saccule and utricle, i ...

in the

inner ear The inner ear (internal ear, auris interna) is the innermost part of the vertebrate ear. In vertebrates, the inner ear is mainly responsible for sound detection and balance. In mammals, it consists of the bony labyrinth, a hollow cavity in the ...

. The

structure A structure is an arrangement and organization of interrelated elements in a material object or system, or the object or system so organized. Material structures include man-made objects such as buildings and machines and natural objects such as ...

of otopetrin-1 (OTOP1) was predicted to include 12

transmembrane domain A transmembrane domain (TMD, TM domain) is a membrane-spanning protein domain. TMDs may consist of one or several alpha-helices or a transmembrane beta barrel. Because the interior of the lipid bilayer is hydrophobic, the amino acid residues in ...

s, with three conserved sub- domains (OD-1 to OD-III). Recently the structures of OTOP1 and OTOP3 were solved by

CryoEM Cryogenic electron microscopy (cryo-EM) is a transmission electron microscopy technique applied to samples cooled to cryogenic temperatures. For biological specimens, the structure is preserved by embedding in an environment of phases of ice#Cry ...

, which showed that the protein assembles as a dimer. The first six transmembrane domains (N-terminal domain) and the second six transmembrane domains (C-terminal) share structural similarity, such that the assembled channel adopts a pseudotetrameric stoichiometry. A permeation pathway for ions is not clear in the solved structures, which show that the central cavity is filled with lipids. Molecular dynamic simulations show that protons may permeate the channel through the N terminal domain, C terminal domain, or the interface of the two domains. Otopetrins were initially thought to modulate

calcium Calcium is a chemical element; it has symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar to it ...

homeostasis In biology, homeostasis (British English, British also homoeostasis; ) is the state of steady internal physics, physical and chemistry, chemical conditions maintained by organism, living systems. This is the condition of optimal functioning fo ...

and influx of

in response to

extracellular This glossary of biology terms is a list of definitions of fundamental terms and concepts used in biology, the study of life and of living organisms. It is intended as introductory material for novices; for more specific and technical definitions ...

ATP but were subsequently shown to form proton-selective ion channels. Otopetrin 1 (OTOP1) is required for normal formation of

in the

. Otoconia are minute biomineral particles embedded in a gelatinous membrane that overlies the sensory

epithelium Epithelium or epithelial tissue is a thin, continuous, protective layer of cells with little extracellular matrix. An example is the epidermis, the outermost layer of the skin. Epithelial ( mesothelial) tissues line the outer surfaces of man ...

in the inner ear.

Gravity In physics, gravity (), also known as gravitation or a gravitational interaction, is a fundamental interaction, a mutual attraction between all massive particles. On Earth, gravity takes a slightly different meaning: the observed force b ...

and

acceleration In mechanics, acceleration is the Rate (mathematics), rate of change of the velocity of an object with respect to time. Acceleration is one of several components of kinematics, the study of motion. Accelerations are Euclidean vector, vector ...

cause the octoconia to deflect the

stereocilia Stereocilia (or stereovilli or villi) are non-motile apical cell modifications. They are distinct from cilia and microvilli, but are closely related to microvilli. They form single "finger-like" projections that may be branched, with normal cel ...

of sensory hair cells. Otoconia are required for processing of information regarding spatial orientation and acceleration. OTOP1 was identified as a candidate for the sour receptor in mice in 2018 and its function as a sour receptor was confirmed in subsequent studies. Despite serving as a sour taste receptor, OTOP1 is not essential for mice to respond to and avoid sour tastes.

References

Further reading