UNC119 is required for G protein trafficking in sensory neurons.
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Zhang H, Constantine R, Vorobiev S, Chen Y, Seetharaman J, Huang YJ, Xiao R, Montelione GT, Gerstner CD, Davis MW, Inana G, Whitby FG, Jorgensen EM, Hill CP, Tong L, Baehr W
UNC119 is required for G protein trafficking in sensory neurons.
Nat Neurosci. 2011 Jun 5;14(7):874-80. doi: 10.1038/nn.2835.
- PubMed ID
- 21642972 [ View in PubMed]
- Abstract
UNC119 is widely expressed among vertebrates and other phyla. We found that UNC119 recognized the acylated N terminus of the rod photoreceptor transducin alpha (Talpha) subunit and Caenorhabditis elegans G proteins ODR-3 and GPA-13. The crystal structure of human UNC119 at 1.95-A resolution revealed an immunoglobulin-like beta-sandwich fold. Pulldowns and isothermal titration calorimetry revealed a tight interaction between UNC119 and acylated Galpha peptides. The structure of co-crystals of UNC119 with an acylated Talpha N-terminal peptide at 2.0 A revealed that the lipid chain is buried deeply into UNC119's hydrophobic cavity. UNC119 bound Talpha-GTP, inhibiting its GTPase activity, thereby providing a stable UNC119-Talpha-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 Galpha subunit cofactor essential for G protein trafficking in sensory cilia.