PUBLICATION

Integrin α8 and Pcdh15 act as a complex to regulate cilia biogenesis in sensory cells

Authors
Goodman, L., Zallocchi, M.
ID
ZDB-PUB-171103-15
Date
2017
Source
Journal of Cell Science   130: 3698-3712 (Journal)
Registered Authors
Keywords
Integrin α8, Pcdh15, Sensory cilia, Usher syndrome
MeSH Terms
  • Hair Cells, Auditory/metabolism*
  • Hair Cells, Auditory/ultrastructure
  • Gene Expression Regulation, Developmental
  • Centrioles/metabolism
  • Centrioles/ultrastructure
  • Endocytosis
  • Integrins/antagonists & inhibitors
  • Integrins/deficiency
  • Integrins/genetics*
  • RNA, Small Interfering/genetics
  • RNA, Small Interfering/metabolism
  • Animals
  • Mutation
  • Zebrafish/genetics*
  • Zebrafish/growth & development
  • Zebrafish/metabolism
  • Signal Transduction
  • Larva/genetics
  • Larva/growth & development
  • Larva/metabolism
  • Usher Syndromes/genetics
  • Usher Syndromes/metabolism
  • Usher Syndromes/pathology
  • Protein Binding
  • rab GTP-Binding Proteins/genetics
  • rab GTP-Binding Proteins/metabolism
  • Disease Models, Animal
  • Humans
  • Actin Cytoskeleton/metabolism
  • Actin Cytoskeleton/ultrastructure
  • Monomeric GTP-Binding Proteins/genetics
  • Monomeric GTP-Binding Proteins/metabolism
  • Cilia/metabolism*
  • Cilia/ultrastructure
  • Cadherins/antagonists & inhibitors
  • Cadherins/deficiency
  • Cadherins/genetics*
  • Zebrafish Proteins/antagonists & inhibitors
  • Zebrafish Proteins/deficiency
  • Zebrafish Proteins/genetics*
  • Zebrafish Proteins/metabolism
(all 41)
PubMed
28883094 Full text @ J. Cell Sci.
Abstract
The way an organism perceives its surroundings depends on sensory systems and the highly specialized cilia present in the neurosensory cells. Here, we describe the existence of an integrin α8 (Itga8) and protocadherin-15a (Pcdh15a) ciliary complex in neuromast hair cells in a zebrafish model. Depletion of the complex via downregulation or loss-of-function mutation leads to a dysregulation of cilia biogenesis and endocytosis. At the molecular level, removal of the complex blocks the access of Rab8a into the cilia as well as normal recruitment of ciliary cargo by centriolar satellites. These defects can be reversed by the introduction of a constitutively active form of Rhoa, suggesting that Itga8-Pcdh15a complex mediates its effect through the activation of this small GTPase and probably by the regulation of actin cytoskeleton dynamics. Our data points to a novel mechanism involved in the regulation of sensory cilia development, with the corresponding implications for normal sensory function.
Genes / Markers
Figures
Figure Gallery (13 images) / 2
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
tc256e
    Point Mutation
    tc320b
      Point Mutation
      th263b
        Point Mutation
        1 - 3 of 3
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        Human Disease / Model
        No data available
        Sequence Targeting Reagents
        Target Reagent Reagent Type
        itga8MO1-itga8MRPHLNO
        itga8MO2-itga8MRPHLNO
        pcdh15aMO1-pcdh15aMRPHLNO
        rhoabMO4-rhoabMRPHLNO
        rhocbMO1-rhocbMRPHLNO
        1 - 5 of 5
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        Fish
        Antibodies
        Orthology
        No data available
        Engineered Foreign Genes
        No data available
        Mapping
        No data available