The interplay between RPGR, PDEδ and Arl2/3 regulate the ciliary targeting of farnesylated cargo

EMBO Rep. 2013 May;14(5):465-72. doi: 10.1038/embor.2013.37. Epub 2013 Apr 5.


Defects in primary cilia result in human diseases known as ciliopathies. The retinitis pigmentosa GTPase regulator (RPGR), mutated in the most severe form of the eye disease, is located at the transition zone of the ciliary organelle. The RPGR-interacting partner PDEδ is involved in trafficking of farnesylated ciliary cargo, but the significance of this interaction is unknown. The crystal structure of the propeller domain of RPGR shows the location of patient mutations and how they perturb the structure. The RPGR·PDEδ complex structure shows PDEδ on a highly conserved surface patch of RPGR. Biochemical experiments and structural considerations show that RPGR can bind with high affinity to cargo-loaded PDEδ and exposes the Arl2/Arl3-binding site on PDEδ. On the basis of these results, we propose a model where RPGR is acting as a scaffold protein recruiting cargo-loaded PDEδ and Arl3 to release lipidated cargo into cilia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADP-Ribosylation Factors / chemistry*
  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Cilia / physiology
  • Conserved Sequence
  • Crystallography, X-Ray
  • Cyclic Nucleotide Phosphodiesterases, Type 6 / chemistry*
  • Eye Proteins / chemistry*
  • Eye Proteins / genetics
  • GTP-Binding Proteins / chemistry*
  • Humans
  • Lipid Metabolism
  • Mice
  • Models, Molecular
  • Mutation, Missense
  • Protein Binding
  • Protein Interaction Domains and Motifs
  • Protein Prenylation
  • Protein Structure, Quaternary
  • Protein Structure, Secondary
  • Protein Transport


  • Eye Proteins
  • RPGR protein, human
  • PDE6D protein, human
  • Cyclic Nucleotide Phosphodiesterases, Type 6
  • Arl2 protein, mouse
  • GTP-Binding Proteins
  • Arl3 protein, mouse
  • ADP-Ribosylation Factors

Associated data

  • PDB/4JHN
  • PDB/4JHP