Ciliopathy genes are required for apical secretion of Cochlin, an otolith crystallization factor
- Leventea, E., Zhu, Z., Fang, X., Nikolaeva, Y., Markham, E., Hirst, R.A., van Eeden, F.J.M., Malicki, J.J.
- Proceedings of the National Academy of Sciences of the United States of America 118(28): (Journal)
- Registered Authors
- Malicki, Jarema, Markham, Elenor R.
- Cochlin, apical secretion, cep290, ear, otolith
- MeSH Terms
- Amino Acid Sequence
- Bardet-Biedl Syndrome/genetics
- Base Sequence
- Epistasis, Genetic
- Gene Expression Regulation, Developmental
- Otolithic Membrane/metabolism*
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- 34244442 Full text @ Proc. Natl. Acad. Sci. USA
Leventea, E., Zhu, Z., Fang, X., Nikolaeva, Y., Markham, E., Hirst, R.A., van Eeden, F.J.M., Malicki, J.J. (2021) Ciliopathy genes are required for apical secretion of Cochlin, an otolith crystallization factor. Proceedings of the National Academy of Sciences of the United States of America. 118(28):.
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.
Genes / Markers
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes