BAI1 localizes AMPA receptors at the cochlear afferent post-synaptic density and is essential for hearing.

Autor:	Carlton AJ; School of Biosciences, University of Sheffield, Sheffield S10 2TN, UK., Jeng JY; School of Biosciences, University of Sheffield, Sheffield S10 2TN, UK., Grandi FC; Sorbonne Université, INSERM, Institute de Myologie, Centre de Recherche en Myologie, 75013 Paris, France., De Faveri F; School of Biosciences, University of Sheffield, Sheffield S10 2TN, UK., Amariutei AE; School of Biosciences, University of Sheffield, Sheffield S10 2TN, UK., De Tomasi L; School of Biosciences, University of Sheffield, Sheffield S10 2TN, UK., O'Connor A; School of Biosciences, University of Sheffield, Sheffield S10 2TN, UK., Johnson SL; School of Biosciences, University of Sheffield, Sheffield S10 2TN, UK; Neuroscience Institute, University of Sheffield, Sheffield S10 2TN, UK., Furness DN; School of Life Sciences, Keele University, Keele ST5 5BG, UK., Brown SDM; Mammalian Genetics Unit, MRC Harwell Institute, Harwell Campus, Oxfordshire OX11 0RD, UK., Ceriani F; School of Biosciences, University of Sheffield, Sheffield S10 2TN, UK., Bowl MR; Mammalian Genetics Unit, MRC Harwell Institute, Harwell Campus, Oxfordshire OX11 0RD, UK., Mustapha M; School of Biosciences, University of Sheffield, Sheffield S10 2TN, UK; Neuroscience Institute, University of Sheffield, Sheffield S10 2TN, UK., Marcotti W; School of Biosciences, University of Sheffield, Sheffield S10 2TN, UK; Neuroscience Institute, University of Sheffield, Sheffield S10 2TN, UK. Electronic address: w.marcotti@sheffield.ac.uk.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2024 Apr 23; Vol. 43 (4), pp. 114025. Date of Electronic Publication: 2024 Apr 01.
DOI:	10.1016/j.celrep.2024.114025
Abstrakt:	Type I spiral ganglion neurons (SGNs) convey sound information to the central auditory pathway by forming synapses with inner hair cells (IHCs) in the mammalian cochlea. The molecular mechanisms regulating the formation of the post-synaptic density (PSD) in the SGN afferent terminals are still unclear. Here, we demonstrate that brain-specific angiogenesis inhibitor 1 (BAI1) is required for the clustering of AMPA receptors GluR2-4 (glutamate receptors 2-4) at the PSD. Adult Bai1-deficient mice have functional IHCs but fail to transmit information to the SGNs, leading to highly raised hearing thresholds. Despite the almost complete absence of AMPA receptor subunits, the SGN fibers innervating the IHCs do not degenerate. Furthermore, we show that AMPA receptors are still expressed in the cochlea of Bai1-deficient mice, highlighting a role for BAI1 in trafficking or anchoring GluR2-4 to the PSDs. These findings identify molecular and functional mechanisms required for sound encoding at cochlear ribbon synapses. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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