ArticleMammalian genome : official journal of the International Mammalian Genome Society2016
The GPSM2/LGN GoLoco motifs are essential for hearing.
Article in Mammalian genome : official journal of the International Mammalian Genome Society, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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30 citing papers in PubMed, 42 citations in OpenAlex.
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- Junctional force patterning drives both positional order and planar polarity in the auditory epithelia.Nature communications · 2025Article
- Whole exome sequencing reveals novel and rare variants in nonsyndromic hearing loss-related genes: A focus onJournal of biosciences · 2025Article
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- RGS12 polarizes the GPSM2-GNAI complex to organize and elongate stereocilia in sensory hair cells.Science advances · 2022Article
- Truncated isoforms of GPSM2 containing the GoLoco motif region promote CD4Lupus science & medicine · 2022Article
- Promotion of row 1-specific tip complex condensates by Gpsm2-Gαi provides insights into row identity of the tallest stereocilia.Science advances · 2022Article
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- Multiple PDZ domain protein maintains patterning of the apical cytoskeleton in sensory hair cells.Development (Cambridge, England) · 2021Article
- EMX2-GPR156-Gαi reverses hair cell orientation in mechanosensory epithelia.Nature communications · 2021Article
- A Reversal in Hair Cell Orientation Organizes Both the Auditory and Vestibular Organs.Frontiers in neuroscience · 2021Review
- Intersection of two key signal integrators in the cell: activator of G-protein signaling 3 and dishevelled-2.Journal of cell science · 2020Article
- Genomic analysis of inherited hearing loss in the Palestinian population.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Development of the cochlea.Development (Cambridge, England) · 2020Review
- Development and Patterning of the Cochlea: From Convergent Extension to Planar Polarity.Cold Spring Harbor perspectives in medicine · 2020Review
- Striatin Is Required for Hearing and Affects Inner Hair Cells and Ribbon Synapses.Frontiers in cell and developmental biology · 2020Article
- New insights into regulation and function of planar polarity in the inner ear.Neuroscience letters · 2019Review
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Authors and funding
15 authors at 5 institutions in 4 countries.
Funding
Abstract
The planar cell polarity (PCP) pathway is responsible for polarizing and orienting cochlear hair cells during development through movement of a primary cilium, the kinocilium. GPSM2/LGN, a mitotic spindle-orienting protein associated with deafness in humans, is a PCP effector involved in kinocilium migration. Here, we link human and mouse truncating mutations in the GPSM2/LGN gene, both leading to hearing loss. The human variant, p.(Trp326*), was identified by targeted genomic enrichment of genes associated with deafness, followed by massively parallel sequencing. Lgn (ΔC) mice, with a targeted deletion truncating the C-terminal GoLoco motifs, are profoundly deaf and show misorientation of the hair bundle and severe malformations in stereocilia shape that deteriorates over time. Full-length protein levels are greatly reduced in mutant mice, with upregulated mRNA levels. The truncated Lgn (ΔC) allele is translated in vitro, suggesting that mutant mice may have partially functioning Lgn. Gαi and aPKC, known to function in the same pathway as Lgn, are dependent on Lgn for proper localization. The polarization of core PCP proteins is not affected in Lgn mutants; however, Lgn and Gαi are misoriented in a PCP mutant, supporting the role of Lgn as a PCP effector. The kinocilium, previously shown to be dependent on Lgn for robust localization, is essential for proper localization of Lgn, as well as Gαi and aPKC, suggesting that cilium function plays a role in positioning of apical proteins. Taken together, our data provide a mechanism for the loss of hearing found in human patients with GPSM2/LGN variants.
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