Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 118, Issue 28, Pages -Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.2102562118
Keywords
cep290; Cochlin; ear; apical secretion; otolith
Categories
Funding
- Biotechnology and Biological Sciences Research Council [BB/R005192/1, BB/R015457/1]
- Medical Research Council [MR/N000714/1]
- Zebrafish Behavioural Unit
- BBSRC [BB/R015457/1, BB/R005192/1] Funding Source: UKRI
- MRC [MR/N000714/1] Funding Source: UKRI
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This study reveals that ciliary proteins play a crucial role in secretion polarity, especially in regulating the secretion of Cochlin, affecting otolith crystallization and behavioral defects.
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.
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