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School of Medicine




Primary cilia are microtubule-based organelles, which protrude from the plasma membrane and receive a wide range of extracellular signals. Various cilia use G protein-coupled receptors (GPCRs) for the detection of these signals. For instance, vertebrate rod photoreceptors use their cilia (also called outer segments) as antennae detecting photons by GPCR rhodopsin. Rhodopsin recognizes incoming light and activates its G protein, transducin, which is composed of three subunits α, β, and γ. Similar to all G protein γ subunits, the transducin Gγ1 subunit undergoes C-terminal prenylation resulting in the addition of an isoprenoid farnesyl; however, the significance of this posttranslational modification is unclear. To study the role of the farnesyl group, we genetically introduced a mutant Gγ1 that lacked the prenylation site into the retinal photoreceptors of mice. The biochemical and physiological analyses of these mice revealed that mutant Gγ1 dimerizes with the endogenous transducin Gβ1 subunit and that the resulting Gβγ dimers display reduced hydrophobicity. Although mutant Gβγ dimers could form a heterotrimeric G protein, they could not mediate phototransduction. This deficiency was due to a strong exclusion of non-farnesylated Gβγ complexes from the cilia (rod outer segments). Our results provide the first evidence that farnesylation is required for trafficking of G-protein βγ subunits to the cilium of rod photoreceptors.

Source Citation

Brooks C, Murphy J, Belcastro M, Heller D, Kolandaivelu S, Kisselev O and Sokolov M (2018) Farnesylation of the Transducin G Protein Gamma Subunit Is a Prerequisite for Its Ciliary Targeting in Rod Photoreceptors. Front. Mol. Neurosci. 11:16. doi: 10.3389/fnmol.2018.00016


Copyright © 2018 Brooks, Murphy, Belcastro, Heller, Kolandaivelu, Kisselev and Sokolov. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.



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