A complex of BBS1 and NPHP7 is required for cilia motility in zebrafish

PLoS One. 2013 Sep 12;8(9):e72549. doi: 10.1371/journal.pone.0072549. eCollection 2013.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cilia / metabolism*
  • Cilia / physiology*
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Protein Binding
  • Zebrafish
  • Zebrafish Proteins / genetics
  • Zebrafish Proteins / metabolism*

Substances

  • Bbs1 protein, zebrafish
  • Nuclear Proteins
  • Zebrafish Proteins

Grants and funding

This study was supported by Deutsche Forschungsgemeinschaft KFO201 (http://www.dfg.de/foerderung/programme/listen/projektdetails/index.jsp?id=58488057) (AK and GW), Excellence Initiative of the German Federal and State Governments (GSC-4, Spemann Graduate School, http://www.sgbm.uni-freiburg.de/) (YK). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.