PUBLICATION

Ciliopathy genes are required for apical secretion of Cochlin, an otolith crystallization factor

Authors
Leventea, E., Zhu, Z., Fang, X., Nikolaeva, Y., Markham, E., Hirst, R.A., van Eeden, F.J.M., Malicki, J.J.
ID
ZDB-PUB-211216-18
Date
2021
Source
Proceedings of the National Academy of Sciences of the United States of America   118(28): (Journal)
Registered Authors
Malicki, Jarema, Markham, Elenor R.
Keywords
Cochlin, apical secretion, cep290, ear, otolith
MeSH Terms
  • Amino Acid Sequence
  • Animals
  • Mutation/genetics
  • Otolithic Membrane/metabolism*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
  • Base Sequence
  • Homozygote
  • Phenotype
  • Cilia/metabolism
  • Epistasis, Genetic
  • Zebrafish/genetics*
  • Bardet-Biedl Syndrome/genetics
  • Ciliopathies/genetics*
  • Crystallization
  • Gene Expression Regulation, Developmental
(all 16)
PubMed
34244442 Full text @ Proc. Natl. Acad. Sci. USA
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.
Genes / Markers
Figures
Figure Gallery (5 images)
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
sa1383
    Point Mutation
    sa2952
      Point Mutation
      sa14425
        Point Mutation
        sh535
          Small Deletion
          sh536
            Small Deletion
            sh555
              Small Deletion
              sh556
                Small Deletion
                sh664TgTransgenic Insertion
                  tz288
                    Point Mutation
                    1 - 9 of 9
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                    Human Disease / Model
                    No data available
                    Sequence Targeting Reagents
                    1 - 8 of 8
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                    Fish
                    Antibodies
                    Orthology
                    No data available
                    Engineered Foreign Genes
                    Marker Marker Type Name
                    EGFPEFGEGFP
                    1 - 1 of 1
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                    Mapping
                    No data available