Distribution of ciliary adaptor proteins tubby and TULP3 in the organ of Corti

Tubby-like proteins are membrane-associated adaptors that mediate directional trafficking into primary cilia. In inner ear sensory epithelia, cilia—including the hair cell’s kinocilium—play important roles as organizers of polarity, tissue architecture and cellular function. However, auditory dysfun...

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Main Authors: Laura A. Lindner, Dennis Derstroff, Dominik Oliver, Katrin Reimann
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-04-01
Series:Frontiers in Neuroscience
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fnins.2023.1162937/full
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author Laura A. Lindner
Dennis Derstroff
Dominik Oliver
Katrin Reimann
author_facet Laura A. Lindner
Dennis Derstroff
Dominik Oliver
Katrin Reimann
author_sort Laura A. Lindner
collection DOAJ
description Tubby-like proteins are membrane-associated adaptors that mediate directional trafficking into primary cilia. In inner ear sensory epithelia, cilia—including the hair cell’s kinocilium—play important roles as organizers of polarity, tissue architecture and cellular function. However, auditory dysfunction in tubby mutant mice was recently found to be related to a non-ciliary function of tubby, the organization of a protein complex in sensory hair bundles of auditory outer hair cells (OHCs). Targeting of signaling components into cilia in the cochlea might therefore rather rely on closely related tubby-like proteins (TULPs). In this study, we compared cellular and subcellular localization of tubby and TULP3 in the mouse inner ear sensory organs. Immunofluorescence microscopy confirmed the previously reported highly selective localization of tubby in the stereocilia tips of OHCs and revealed a previously unnoticed transient localization to kinocilia during early postnatal development. TULP3 was detected in the organ of Corti and vestibular sensory epithelium, where it displayed a complex spatiotemporal pattern. TULP3 localized to kinocilia of cochlear and vestibular hair cells in early postnatal development but disappeared subsequently before the onset of hearing. This pattern suggested a role in targeting ciliary components into kinocilia, possibly related to the developmental processes that shape the sensory epithelia. Concurrent with loss from kinocilia, pronounced TULP3 immunolabeling progressively appeared at microtubule bundles in non-sensory Pillar (PCs) and Deiters cells (DC). This subcellular localization may indicate a novel function of TULP proteins associated with the formation or regulation of microtubule-based cellular structures.
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spelling doaj.art-dcb7e78f75cc41fc8de3c1772594f4af2023-04-18T05:24:46ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2023-04-011710.3389/fnins.2023.11629371162937Distribution of ciliary adaptor proteins tubby and TULP3 in the organ of CortiLaura A. Lindner0Dennis Derstroff1Dominik Oliver2Katrin Reimann3Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Marburg, Philipps-University Marburg, Marburg, GermanyDepartment of Otorhinolaryngology, Head and Neck Surgery, University Hospital Marburg, Philipps-University Marburg, Marburg, GermanyDepartment of Neurophysiology, Institute of Physiology and Pathophysiology, Philipps-University Marburg, Marburg, GermanyDepartment of Otorhinolaryngology, Head and Neck Surgery, University Hospital Marburg, Philipps-University Marburg, Marburg, GermanyTubby-like proteins are membrane-associated adaptors that mediate directional trafficking into primary cilia. In inner ear sensory epithelia, cilia—including the hair cell’s kinocilium—play important roles as organizers of polarity, tissue architecture and cellular function. However, auditory dysfunction in tubby mutant mice was recently found to be related to a non-ciliary function of tubby, the organization of a protein complex in sensory hair bundles of auditory outer hair cells (OHCs). Targeting of signaling components into cilia in the cochlea might therefore rather rely on closely related tubby-like proteins (TULPs). In this study, we compared cellular and subcellular localization of tubby and TULP3 in the mouse inner ear sensory organs. Immunofluorescence microscopy confirmed the previously reported highly selective localization of tubby in the stereocilia tips of OHCs and revealed a previously unnoticed transient localization to kinocilia during early postnatal development. TULP3 was detected in the organ of Corti and vestibular sensory epithelium, where it displayed a complex spatiotemporal pattern. TULP3 localized to kinocilia of cochlear and vestibular hair cells in early postnatal development but disappeared subsequently before the onset of hearing. This pattern suggested a role in targeting ciliary components into kinocilia, possibly related to the developmental processes that shape the sensory epithelia. Concurrent with loss from kinocilia, pronounced TULP3 immunolabeling progressively appeared at microtubule bundles in non-sensory Pillar (PCs) and Deiters cells (DC). This subcellular localization may indicate a novel function of TULP proteins associated with the formation or regulation of microtubule-based cellular structures.https://www.frontiersin.org/articles/10.3389/fnins.2023.1162937/fullphosphoinositidestubbyTULP3hair cellsorgan of Cortiimmunohistochemistry
spellingShingle Laura A. Lindner
Dennis Derstroff
Dominik Oliver
Katrin Reimann
Distribution of ciliary adaptor proteins tubby and TULP3 in the organ of Corti
Frontiers in Neuroscience
phosphoinositides
tubby
TULP3
hair cells
organ of Corti
immunohistochemistry
title Distribution of ciliary adaptor proteins tubby and TULP3 in the organ of Corti
title_full Distribution of ciliary adaptor proteins tubby and TULP3 in the organ of Corti
title_fullStr Distribution of ciliary adaptor proteins tubby and TULP3 in the organ of Corti
title_full_unstemmed Distribution of ciliary adaptor proteins tubby and TULP3 in the organ of Corti
title_short Distribution of ciliary adaptor proteins tubby and TULP3 in the organ of Corti
title_sort distribution of ciliary adaptor proteins tubby and tulp3 in the organ of corti
topic phosphoinositides
tubby
TULP3
hair cells
organ of Corti
immunohistochemistry
url https://www.frontiersin.org/articles/10.3389/fnins.2023.1162937/full
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