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Updated: May 27, 2025

Imaging G-protein Coupled Receptor GPCR-mediated Signaling Events that Control Chemotaxis of Dictyostelium Discoideum
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A force-sensitive adhesion GPCR is required for equilibrioception.

Zhao Yang1, Shu-Hua Zhou1,2,3, Qi-Yue Zhang1

  • 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, Shandong, China.

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|February 18, 2025
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Summary
This summary is machine-generated.

The G protein-coupled receptor LPHN2 is essential for balance. This receptor in vestibular hair cells enables mechanoelectrical transduction, crucial for sensing motion and maintaining equilibrium.

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Area of Science:

  • Neuroscience
  • Sensory Biology
  • Molecular Biology

Background:

  • Equilibrioception, or balance sensing, is vital for mammalian navigation.
  • Vestibular hair cells use rapid mechanoelectrical transduction (MET) to detect motion and position.

Purpose of the Study:

  • To identify molecular components essential for balance sensing.
  • To investigate the role of LPHN2 in vestibular hair cell function and equilibrioception.

Main Methods:

  • Utilized hair-cell-specific Lphn2-knockout mice and an LPHN2-specific inhibitor.
  • Performed functional analyses of balance behavior and MET response.
  • Conducted mechanistic studies in a heterologous system to explore LPHN2's function.

Main Results:

  • Loss of LPHN2 in hair cells impaired balance and MET response.
  • LPHN2 regulates tip-link-independent MET currents.
  • LPHN2 converts mechanical force into TMC1 channel activity, triggering neurotransmitter release and calcium signaling.

Conclusions:

  • LPHN2 is a critical mechanosensitive G protein-coupled receptor for mammalian balance.
  • Restoration of LPHN2 in hair cells recovered vestibular function.
  • This study reveals a novel role for a GPCR in sensory transduction for equilibrioception.