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Related Concept Videos

Auditory Perception01:17

Auditory Perception

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The auditory system is essential for sound perception, utilizing various critical structures. When sound waves enter the outer ear, they travel through the ear canal and cause the eardrum to vibrate. These vibrations are then transmitted to the middle ear, where three tiny bones – the malleus, incus, and stapes – amplify the sound. This amplification is crucial, as it ensures that the sound vibrations are strong enough to be conveyed to the inner ear. These vibrations then reach the...
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Auditory Pathway01:15

Auditory Pathway

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Auditory pathways constitute the complex neural circuits responsible for transmitting and interpreting auditory information from the peripheral auditory system to the brain. Sound waves are initially captured by the outer ear, funneled through the ear canal, and reach the tympanic membrane (eardrum). These vibrations are transmitted via the middle ear's ossicles to the inner ear's cochlea.
When viewed cross-sectionally, the cochlea reveals the scala vestibuli and scala tympani flanking...
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Hair Cells01:22

Hair Cells

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Hair cells are the sensory receptors of the auditory system—they transduce mechanical sound waves into electrical energy that the nervous system can understand. Hair cells are located in the organ of Corti within the cochlea of the inner ear, between the basilar and tectorial membranes. The actual sensory receptors are called inner hair cells. The outer hair cells serve other functions, such as sound amplification in the cochlea, and are not discussed in detail here.
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The Cochlea01:13

The Cochlea

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The cochlea is a coiled structure in the inner ear that contains hair cells—the sensory receptors of the auditory system. Sound waves are transmitted to the cochlea by small bones attached to the eardrum called the ossicles, which vibrate the oval window that leads to the inner ear. This causes fluid in the chambers of the cochlea to move, vibrating the basilar membrane.
50.4K
GPCRs Regulate Adenylyl Cylase Activity01:09

GPCRs Regulate Adenylyl Cylase Activity

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Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of...
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G-Protein Gated Ion Channels01:21

G-Protein Gated Ion Channels

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GPCRs are primarily responsible for our sense of smell, taste, and vision.  The binding of a sensory stimulus activates GPCR to stimulate effector proteins, many of which are ion channels in the sensory organs. GPCRs modulate the opening and closing of the target ion channels either directly by binding them, or by releasing second messengers that activate these channels. As ions move across the membrane, the membrane potential is altered, which induces an appropriate response.
Sensory...
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Related Experiment Video

Updated: Jan 12, 2026

Morphological and Functional Evaluation of Ribbon Synapses at Specific Frequency Regions of the Mouse Cochlea
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The force-sensing GPCR LPHN2 is indispensable for normal auditory function.

Shu-Hua Zhou1, Ming-Wei Wang2, Zhi-Chen Song3

  • 1NHC Key Laboratory of Otorhinolaryngology, Qilu Hospital of Shandong University, and New Cornerstone Science Laboratory, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, China; Department of Physiology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, China; State Key Laboratory of Vascular Homeostasis and Remodeling, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, Beijing 100191, China.

Cell Reports
|November 5, 2025
PubMed
Summary
This summary is machine-generated.

Researchers discovered that the G-protein-coupled receptor LPHN2 is crucial for hearing. LPHN2 physically interacts with the TMC1 channel, enabling mechano-electrical transduction and preventing hearing loss in mice.

Keywords:
CP: neuroscienceCochlear hair cellGPCRLPHN2METhearingmechanosensitive

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Last Updated: Jan 12, 2026

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Area of Science:

  • Neuroscience
  • Otolaryngology
  • Molecular Biology

Background:

  • Mechano-electrical transduction (MET) converts mechanical force into electrical signals, essential for hearing.
  • G-protein-coupled receptors (GPCRs) are involved in various cellular processes, but their role in auditory transduction is not fully understood.

Purpose of the Study:

  • To investigate the role of the GPCR LPHN2/ADGRL2 in auditory perception and mechano-electrical transduction.
  • To elucidate the mechanism by which LPHN2 influences MET channels in cochlear hair cells.

Main Methods:

  • Utilized hair-cell-specific gene deficiency models in mice.
  • Employed specific LPHN2 inhibitors to assess MET response.
  • Investigated physical interactions between LPHN2 and TMC1 using biophysical techniques.
  • Analyzed calcium ion (Ca2+) responses and neurotransmitter release.

Main Results:

  • LPHN2 is expressed in cochlear hair cell stereocilia and associates with MET channel components.
  • LPHN2 deficiency in hair cells leads to hearing loss and impaired MET responses.
  • LPHN2 physically interacts with TMC1, inducing conformational changes upon force application.
  • LPHN2 activation stimulates Ca2+ response and neurotransmitter release, and its expression prevents hearing loss in deficient mice.

Conclusions:

  • The GPCR LPHN2 plays a significant modulatory role in auditory processes.
  • LPHN2 functions through a mechanism coupled to the TMC1 channel for force sensing.
  • This discovery offers insights into the molecular mechanisms underlying hearing and potential therapeutic targets for hearing loss.