ArticleProceedings of the National Academy of Sciences of the United States of America2025
SHANK2 establishes auditory hair bundle architecture essential for mammalian hearing.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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1 citing paper in PubMed.
- Emerging Potential of Ras-proximate-1 (Rap1) in Mediating Neurodegenerative Diseases.Current neuropharmacology · 2026Review
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12 authors.
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Abstract
The mammalian auditory system relies on the precise architecture of the hair cell stereociliary bundle for effective sound transduction. Each bundle consists of approximately 100 actin-filled stereocilia arranged in a three-row staircase pattern, forming a linear shape in inner hair cells (IHCs) and a V-shape in outer hair cells (OHCs), the latter geometry being a hallmark of the mammalian cochlea. While the initial development from uniformly distributed microvilli into stereociliary bundles is guided by lateral migration of the kinocilium, the mechanisms that establish the characteristic bundle architecture and its functional significance remain unclear. Here, we show that SHANK2, a protein implicated in synaptic function and autism spectrum disorders, is a critical regulator of bundle architecture. SHANK2 localizes to the medial apical surface of developing hair cells. This localization is regulated by the small GTPase RAP1, independently of known lateral (Gαi, GPSM2) or medial (aPKCζ, PARD6B) proteins. Hair cell-specific ablation of
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