PUBLICATION

A Complex of BBS1 and NPHP7 Is Required for Cilia Motility in Zebrafish

Authors
Kim, Y.H., Epting, D., Slanchev, K., Engel, C., Walz, G., and Kramer-Zucker, A.
ID
ZDB-PUB-131025-1
Date
2013
Source
PLoS One   8(9): e72549 (Journal)
Registered Authors
Epting, Daniel, Kim, Yun Hee, Kramer-Zucker, Albrecht, Slanchev, Krasimir
Keywords
none
MeSH Terms
  • Animals
  • Cilia/metabolism*
  • Cilia/physiology*
  • Nuclear Proteins/genetics
  • Nuclear Proteins/metabolism*
  • Protein Binding
  • Zebrafish
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed
24069149 Full text @ PLoS One
Abstract

Bardet-Biedl syndrome (BBS) and nephronophthisis (NPH) are hereditary autosomal recessive disorders, encoded by two families of diverse genes. BBS and NPH display several overlapping phenotypes including cystic kidney disease, retinitis pigmentosa, liver fibrosis, situs inversus and cerebellar defects. Since most of the BBS and NPH proteins localize to cilia and/or their appendages, BBS and NPH are considered ciliopathies. In this study, we characterized the function of the transcription factor Nphp7 in zebrafish, and addressed the molecular connection between BBS and NPH. The knockdown of zebrafish bbs1 and nphp7.2 caused similar phenotypic changes including convergent extension defects, curvature of the body axis, hydrocephalus, abnormal heart looping and cystic pronephros, all consistent with an altered ciliary function. Immunoprecipitation assays revealed a physical interaction between BBS1 and NPHP7, and the simultaneous knockdown of zbbs1 and znphp7.2 enhanced the cystic pronephros phenotype synergistically, suggesting a genetic interaction between zbbs1 and znphp7.2 in vivo. Deletion of zBbs1 or zNphp7.2 did not compromise cilia formation, but disrupted cilia motility. Although NPHP7 has been shown to act as transcriptional repressor, our studies suggest a crosstalk between BBS1 and NPHP7 in regulating normal function of the cilium.

Genes / Markers
Figures
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes