Abstract
Appropriate physiological signaling by primary cilia depends on the specific targeting of particular receptors to the ciliary membrane, but how this occurs remains poorly understood. In this study, we show that D1-type dopaminergic receptors are delivered to cilia from the extra-ciliary plasma membrane by a mechanism requiring the receptor cytoplasmic tail, the intraflagellar transport complex-B (IFT-B), and ciliary kinesin KIF17. This targeting mechanism critically depends on Rab23, a small guanine nucleotide binding protein that has important effects on physiological signaling from cilia but was not known previously to be essential for ciliary delivery of any cargo. Depleting Rab23 prevents dopamine receptors from accessing the ciliary membrane. Conversely, fusion of Rab23 to a non-ciliary receptor is sufficient to drive robust, nucleotide-dependent mis-localization to the ciliary membrane. Dopamine receptors thus reveal a previously unrecognized mechanism of ciliary receptor targeting and functional role of Rab23 in promoting this process.
Highlights
Primary cilia are microtubule-based protrusions of the plasma membrane that support a wide range of specialized receptor-mediated signaling functions
We show that the D1R cytoplasmic tail is both necessary and sufficient to direct receptor targeting to the ciliary membrane, and this requires a distinct set of cellular proteins including the anterograde intraflagellar transport complex-B (IFT-B) complex and ciliary kinesin, KIF17
Using an N-terminal Flag tag on the D1R to label the overall surface pool, D1Rs were visualized throughout the plasma membrane and highly enriched in cilia marked by acetylated tubulin (AcTub) (Figure 1A), like the cilia-localized somatostatin-3 receptor (SSTR3) (Figure 1B; Handel et al, 1999; Schulz et al, 2000; Berbari et al, 2008a)
Summary
Primary cilia are microtubule-based protrusions of the plasma membrane that support a wide range of specialized receptor-mediated signaling functions. The ciliary membrane compartment is separated from the surrounding extra-ciliary plasma membrane by a transition zone complex that impedes lateral exchange of membrane proteins (Gilula and Satir, 1972; Hu et al, 2010; Chih et al, 2011; Williams et al, 2011). This can explain how GPCRs are retained in cilia once delivered, but not how they are delivered in the first place.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
