UNC119 is required for G protein trafficking in sensory neurons

Houbin Zhang, Ryan Constantine, Sergey Vorobiev, Yang Chen, Jayaraman Seetharaman, Yuanpeng Janet Huang, Rong Xiao, Gaetano T. Montelione, Cecilia D. Gerstner, M. Wayne Davis, George Inana, Frank G. Whitby, Erik M. Jorgensen, Christopher P. Hill, Liang Tong, Wolfgang Baehr

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103 Scopus citations

Abstract

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-Ã.. resolution revealed an immunoglobulin-like α2-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 UNC119-2s 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 GÎ ± subunit cofactor essential for G protein trafficking in sensory cilia.

Original languageEnglish
Pages (from-to)874-880
Number of pages7
JournalNature Neuroscience
Volume14
Issue number7
DOIs
StatePublished - Jul 1 2011

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ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Zhang, H., Constantine, R., Vorobiev, S., Chen, Y., Seetharaman, J., Huang, Y. J., Xiao, R., Montelione, G. T., Gerstner, C. D., Davis, M. W., Inana, G., Whitby, F. G., Jorgensen, E. M., Hill, C. P., Tong, L., & Baehr, W. (2011). UNC119 is required for G protein trafficking in sensory neurons. Nature Neuroscience, 14(7), 874-880. https://doi.org/10.1038/nn.2835