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Ciliopathy genes are required for apical secretion of Cochlin, an otolith crystallization factor
- Source :
- Proc Natl Acad Sci U S A
- Publication Year :
- 2021
- Publisher :
- National Academy of Sciences, 2021.
-
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.
- Subjects :
- 0301 basic medicine
Ciliopathies
03 medical and health sciences
Otolithic Membrane
0302 clinical medicine
medicine
Animals
Secretion
Amino Acid Sequence
Cilia
Bardet-Biedl Syndrome
Secretory pathway
Zebrafish
Vestibular system
Extracellular Matrix Proteins
Multidisciplinary
Base Sequence
Chemistry
Cilium
Homozygote
Gene Expression Regulation, Developmental
Epistasis, Genetic
Biological Sciences
Zebrafish Proteins
medicine.disease
Cell biology
Transport protein
Ciliopathy
030104 developmental biology
medicine.anatomical_structure
Phenotype
Mutation
Basal lamina
sense organs
Crystallization
030217 neurology & neurosurgery
Subjects
Details
- Language :
- English
- ISSN :
- 00278424
- Database :
- OpenAIRE
- Journal :
- Proc Natl Acad Sci U S A
- Accession number :
- edsair.doi.dedup.....64719ef8ce7d89ba4d4526a3b7a444a1