UNC119 is required for G protein trafficking in sensory neurons
- 5 June 2011
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Neuroscience
- Vol. 14 (7), 874-880
- https://doi.org/10.1038/nn.2835
Abstract
UNC119 is a protein localized to the non-motile primary cilia. Here, Zhang et al. report the crystal structure of UNC119 and provide biochemical and cellular evidence that UNC119 is a lipid-binding protein that mediates G protein trafficking. The authors also show that that UNC119 function is conserved from GPCR trafficking in C. elegans olfactory neuron to transducin trafficking in mammalian photoreceptors. 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.Keywords
This publication has 55 references indexed in Scilit:
- The Conserved Bardet-Biedl Syndrome Proteins Assemble a Coat that Traffics Membrane Proteins to CiliaCell, 2010
- Different Properties of the Native and Reconstituted Heterotrimeric G Protein TransducinBiochemistry, 2008
- RIBEYE Recruits Munc119, a Mammalian Ortholog of the Caenorhabditis elegans Protein unc119, to Synaptic Ribbons of Photoreceptor SynapsesPublished by Elsevier BV ,2008
- Mechanism of light‐induced translocation of arrestin and transducin in photoreceptors: Interaction‐restricted diffusionIUBMB Life, 2007
- The Proteome of the Mouse Photoreceptor Sensory Cilium ComplexMolecular & Cellular Proteomics, 2007
- Assembly and Trafficking of Heterotrimeric G ProteinsBiochemistry, 2007
- Deletion of PrBP/δ impedes transport of GRK1 and PDE6 catalytic subunits to photoreceptor outer segmentsProceedings of the National Academy of Sciences of the United States of America, 2007
- Targeted inactivation of synaptic HRG4 (UNC119) causes dysfunction in the distal photoreceptor and slow retinal degeneration, revealing a new functionExperimental Eye Research, 2007
- Intraflagellar transportNature Reviews Molecular Cell Biology, 2002
- [20] Processing of X-ray diffraction data collected in oscillation modeMethods in Enzymology, 1997