ArticleCellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology2018
Gαi Proteins are Indispensable for Hearing.
Article in Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 38 citations in OpenAlex.
- Article
- Advances in the treatment of age-related hearing loss: from molecular mechanisms to targeted interventions.Frontiers in aging neuroscience · 2026Review
- GαInternational journal of molecular sciences · 2025Article
- 5xFAD mutations induce hearing impairment in the Ahl-corrected 5xFAD mice.Experimental neurology · 2025Article
- Decoding the Functional Interactome of Non-Model Organisms with PHILHARMONIC.bioRxiv : the preprint server for biology · 2025Article
- mRNA metabolism regulator human antigen R (HuR) regulates age-related hearing loss in aged mice.Nature aging · 2025Article
- Proteins required for stereocilia elongation during mammalian hair cell development ensure precise and steady heights during adult life.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Targeting GαBasic research in cardiology · 2024Article
- Article
- Protective effects of GαNaunyn-Schmiedeberg's archives of pharmacology · 2024Article
- miRNA Profiling of Developing Rat Retina in the First Three Postnatal Weeks.Cellular and molecular neurobiology · 2023Article
- Involvement of Dmp1 in the Precise Regulation of Hair Bundle Formation in the Developing Cochlea.Biology · 2023Article
- Loss of Pex1 in Inner Ear Hair Cells Contributes to Cochlear Synaptopathy and Hearing Loss.Cells · 2022Article
- RGS12 polarizes the GPSM2-GNAI complex to organize and elongate stereocilia in sensory hair cells.Science advances · 2022Article
- Promotion of row 1-specific tip complex condensates by Gpsm2-Gαi provides insights into row identity of the tallest stereocilia.Science advances · 2022Article
- Review
- Article
- Daple deficiency causes hearing loss in adult mice by inducing defects in cochlear stereocilia and apical microtubules.Scientific reports · 2021Article
- Multiple PDZ domain protein maintains patterning of the apical cytoskeleton in sensory hair cells.Development (Cambridge, England) · 2021Article
- Analyses of Gnai3-iresGFP reporter mice reveal unknown GαScientific reports · 2021Article
Corrections and comments
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Authors and funding
21 authors at 7 institutions in 6 countries.
Funding
Abstract
BACKGROUND/
aimsFrom invertebrates to mammals, Gαi proteins act together with their common binding partner Gpsm2 to govern cell polarization and planar organization in virtually any polarized cell. Recently, we demonstrated that Gαi3-deficiency in pre-hearing murine cochleae pointed to a role of Gαi3 for asymmetric migration of the kinocilium as well as the orientation and shape of the stereociliary ("hair") bundle, a requirement for the progression of mature hearing. We found that the lack of Gαi3 impairs stereociliary elongation and hair bundle shape in high-frequency cochlear regions, linked to elevated hearing thresholds for high-frequency sound. How these morphological defects translate into hearing phenotypes is not clear.
methodsHere, we studied global and conditional Gnai3 and Gnai2 mouse mutants deficient for either one or both Gαi proteins. Comparative analyses of global versus Foxg1-driven conditional mutants that mainly delete in the inner ear and telencephalon in combination with functional tests were applied to dissect essential and redundant functions of different Gαi isoforms and to assign specific defects to outer or inner hair cells, the auditory nerve, satellite cells or central auditory neurons.
resultsHere we report that lack of Gαi3 but not of the ubiquitously expressed Gαi2 elevates hearing threshold, accompanied by impaired hair bundle elongation and shape in high-frequency cochlear regions. During the crucial reprogramming of the immature inner hair cell (IHC) synapse into a functional sensory synapse of the mature IHC deficiency for Gαi2 or Gαi3 had no impact. In contrast, double-deficiency for Gαi2 and Gαi3 isoforms results in abnormalities along the entire tonotopic axis including profound deafness associated with stereocilia defects. In these mice, postnatal IHC synapse maturation is also impaired. In addition, the analysis of conditional versus global Gαi3-deficient mice revealed that the amplitude of ABR wave IV was disproportionally elevated in comparison to ABR wave I indicating that Gαi3 is selectively involved in generation of neural gain during auditory processing.
conclusionWe propose a so far unrecognized complexity of isoform-specific and overlapping Gαi protein functions particular during final differentiation processes.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.