Leventea, E., Zhu, Z., Fang, X. et al. (5 more authors) (2021) Ciliopathy genes are required for apical secretion of Cochlin, an otolith crystallization factor. Proceedings of the National Academy of Sciences, 118 (28). e2102562118. ISSN 0027-8424
Abstract
Here, we report that important regulators of cilia formation and ciliary compartment–directed protein transport function in secretion polarity. Mutations in cilia genes cep290 and bbs2, involved in human ciliopathies, affect apical secretion of Cochlin, a major otolith component and a determinant of calcium carbonate crystallization form. We show that Cochlin, defective in human auditory and vestibular disorder, DFNA9, is secreted from small specialized regions of vestibular system epithelia. Cells of these regions secrete Cochlin both apically into the ear lumen and basally into the basal lamina. Basally secreted Cochlin diffuses along the basal surface of vestibular epithelia, while apically secreted Cochlin is incorporated into the otolith. Mutations in a subset of ciliopathy genes lead to defects in Cochlin apical secretion, causing abnormal otolith crystallization and behavioral defects. This study reveals a class of ciliary proteins that are important for the polarity of secretion and delineate a secretory pathway that regulates biomineralization.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2021 The Author(s). This is an author-produced version of a paper subsequently published in Proceedings of the National Academy of Sciences. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | cep290; Cochlin; ear; apical secretion; otolith |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Science (Sheffield) > School of Biosciences (Sheffield) > Department of Biomedical Science (Sheffield) |
Funding Information: | Funder Grant number MEDICAL RESEARCH COUNCIL MR/N000714/1 BIOTECHNOLOGY AND BIOLOGICAL SCIENCES RESEARCH COUNCIL BB/R005192/1 BIOTECHNOLOGY AND BIOLOGICAL SCIENCES RESEARCH COUNCIL BB/R015457/1 |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 09 Jul 2021 15:23 |
Last Modified: | 08 Jan 2022 01:39 |
Status: | Published |
Publisher: | National Academy of Sciences |
Refereed: | Yes |
Identification Number: | 10.1073/pnas.2102562118 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:176037 |