PUBLICATION

Cilia localization is essential for in vivo functions of the Joubert syndrome protein Arl13b/Scorpion

Authors
Duldulao, N.A., Lee, S., and Sun, Z.
ID
ZDB-PUB-091120-47
Date
2009
Source
Development (Cambridge, England)   136(23): 4033-4042 (Journal)
Registered Authors
Duldulao, Neil, Lee, Sunjin, Sun, Zhaoxia
Keywords
Arl13b, Scorpion, Cilium, Joubert syndrome, Kidney cyst, Laterality
MeSH Terms
  • ADP-Ribosylation Factors/genetics
  • ADP-Ribosylation Factors/metabolism
  • Alleles
  • Animals
  • Cilia/genetics
  • Cilia/metabolism*
  • Cilia/ultrastructure
  • Embryo, Nonmammalian/ultrastructure
  • Gene Deletion
  • Genes, Recessive
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization
  • Kidney Diseases, Cystic/genetics
  • Kidney Diseases, Cystic/metabolism
  • Mutation
  • Point Mutation
  • Syndrome
  • Zebrafish/genetics
  • Zebrafish/metabolism
  • Zebrafish Proteins/genetics*
  • Zebrafish Proteins/metabolism*
PubMed
19906870 Full text @ Development
Abstract
arl13b was initially cloned as the novel cystic kidney gene scorpion (sco) in zebrafish and was shown to be required for cilia formation in the kidney duct. In mouse, a null mutant of Arl13b shows abnormal ultrastructure of the cilium and defective sonic hedgehog (Shh) signaling. Importantly, a recent study linked mutations in ARL13B to a classical form of Joubert syndrome (JS), an autosomal recessive disorder characterized by a distinctive cerebellar malformation. In this study, we analyzed the zebrafish arl13b (sco) mutant and gene products in detail. We first demonstrate that Arl13b is a protein that is highly enriched in the cilium and is required for cilia formation in multiple organs in zebrafish, and that knockdown of arl13b leads to multiple cilia-associated phenotypes. We additionally show that multiple regions of Arl13b are required for its localization to the cilium. By means of rescuing experiments with a series of deletion and point mutants, we further demonstrate that the ciliary localization is crucial for the in vivo function of Arl13b. Together, these results strongly support the hypothesis that JS-related disease (JSRD) is a ciliopathy, or a disease caused by ciliary defects, and that Arl13b functions mainly through the cilium.
Genes / Markers
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping