UNC119 is required for G protein trafficking in sensory neurons

Nat Neurosci. 2011 Jun 5;14(7):874-80. doi: 10.1038/nn.2835.


UNC119 is widely expressed among vertebrates and other phyla. We found that UNC119 recognized the acylated N terminus of the rod photoreceptor transducin α (Tα) subunit and Caenorhabditis elegans G proteins ODR-3 and GPA-13. The crystal structure of human UNC119 at 1.95-Å resolution revealed an immunoglobulin-like β-sandwich fold. Pulldowns and isothermal titration calorimetry revealed a tight interaction between UNC119 and acylated Gα peptides. The structure of co-crystals of UNC119 with an acylated Tα N-terminal peptide at 2.0 Å revealed that the lipid chain is buried deeply into UNC119's hydrophobic cavity. UNC119 bound Tα-GTP, inhibiting its GTPase activity, thereby providing a stable UNC119-Tα-GTP complex capable of diffusing from the inner segment back to the outer segment after light-induced translocation. UNC119 deletion in both mouse and C. elegans led to G protein mislocalization. Thus, UNC119 is a Gα subunit cofactor essential for G protein trafficking in sensory cilia.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / chemistry
  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • Animals, Genetically Modified
  • Caenorhabditis elegans
  • Caenorhabditis elegans Proteins / genetics
  • Cattle
  • Dark Adaptation / genetics
  • GTP Phosphohydrolases / metabolism
  • GTP-Binding Protein alpha Subunits / deficiency
  • GTP-Binding Protein alpha Subunits / metabolism*
  • GTP-Binding Protein alpha Subunits, G12-G13 / genetics
  • GTP-Binding Protein alpha Subunits, G12-G13 / metabolism
  • GTP-Binding Protein alpha Subunits, Gi-Go
  • Gene Expression Regulation / genetics
  • Gene Expression Regulation / physiology*
  • Glycine / genetics
  • Green Fluorescent Proteins / genetics
  • Humans
  • Mice
  • Mice, Knockout
  • Models, Chemical
  • Models, Molecular
  • Mutation / genetics
  • Protein Binding / genetics
  • Protein Structure, Quaternary / genetics
  • Protein Transport / genetics
  • Sensory Receptor Cells / metabolism*
  • Signal Transduction / genetics
  • Time Factors
  • Transducin / deficiency
  • Transducin / genetics
  • Transducin / metabolism*


  • Adaptor Proteins, Signal Transducing
  • Caenorhabditis elegans Proteins
  • GTP-Binding Protein alpha Subunits
  • Gnat1 protein, mouse
  • UNC119 protein, human
  • odr-3 protein, C elegans
  • Green Fluorescent Proteins
  • GTP Phosphohydrolases
  • GTP-Binding Protein alpha Subunits, G12-G13
  • GTP-Binding Protein alpha Subunits, Gi-Go
  • Transducin
  • Glycine

Associated data

  • PDB/3RBQ