The otopetrin family is a group of proteins 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 movement with balance. Together with the cochlea, a part of the auditory system, it constitutes ...

, 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 the flow of io ...

s expressed in many different tissues, including taste 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/ otoliths 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 domains, 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 cryomicroscopy technique applied on samples cooled to cryogenic temperatures. For biological specimens, the structure is preserved by embedding in an environment of vitreous ice. An aqueous sample sol ...

, 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 homeostasis and influx of calcium in response to extracellular

ATP ATP may refer to: Companies and organizations * Association of Tennis Professionals, men's professional tennis governing body * American Technical Publishers, employee-owned publishing company * ', a Danish pension * Armenia Tree Project, non ...

but were subsequently shown to form proton-selective ion channels. Otopetrin 1 (OTOP1) is required for normal formation of otoconia/ otoliths in the

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

epithelium Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercellul ...

in the inner ear. Gravity and acceleration cause the octoconia to deflect the stereocilia of sensory hair cells. Otoconia are required for processing of information regarding

spatial Spatial may refer to: *Dimension *Space *Three-dimensional space Three-dimensional space (also: 3D space, 3-space or, rarely, tri-dimensional space) is a geometric setting in which three values (called ''parameters'') are required to determ ...

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