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H. Zhang, R. Constantine, M. Davis, G. Inana, E. M. Jorgensen, W. Baehr; Unc119/RG4 Regulates G Protein Trafficking in Sensory Neurons by Recognizing the Acylated G N-Terminus. Invest. Ophthalmol. Vis. Sci. 2010;51(13):1083.
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© ARVO (1962-2015); The Authors (2016-present)
UNC119 (alias HRG4) is a protein with sequence similarity to PrBP/Δ (alias Pde6Δ). It is expressed near ubiquitously from single cell organisms (Paramecium), worms (C. elegans), zebrafish (D. rerio) to human, but is relatively abundant in mammalian photoreceptors. A truncation mutation in the human UNC119 gene was associated with cone dystrophy in human and a mouse model. The purpose of this study was to identify its function in the retina.
GST-pull downs, LC-MS/MS, isothermal titration microcalorimetry (ITC), immunocytochemistry with Unc119 mouse and C.elegans knockouts, transgenic C.elegans unc-119 rescue.
We show that transducin, the G protein required for phototransduction, interacts with UNC119/HRG4, a homolog of C. elegans UNC-119 that is expressed in photoreceptors. Interaction is specific to the N-terminus of the transducin α-subunit (Tα) and requires its acylation. In Unc119-/- photoreceptors, Tα is in part mislocalized to the inner segment. After photobleaching of Unc119-/- retina, translocation of Tα to the dark-adapted outer segment is impeded. In C. elegans unc-119 null mutants, the G proteins ODR-3 and GPA-13 fail to traffic to the cilia of AWA and AWC olfactory neurons. Transgenic expression of UNC-119 under the control of the gpa-13 promoter restores localization of GPA-13 and ODR-3. Thus, UNC119 functions as an acyl-binding protein that is essential for trafficking of G protein α subunits from cell bodies to cilia in sensory neurons.
These results establish that UNC119 functions as a novel acyl binding protein and cofactor/chaperone in transporting a set of peripherally membrane associated G protein α-subunits.
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