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RPGR, a prenylated retinal ciliopathy protein, is targeted to cilia in a prenylation- and PDE6D-dependent manner
Journal article   Open access   Peer reviewed

RPGR, a prenylated retinal ciliopathy protein, is targeted to cilia in a prenylation- and PDE6D-dependent manner

Nirmal Dutta and Seongjin Seo
Biology Open, Vol.5(9), pp.1283-1289
2016
DOI: 10.1242/bio.020461
PMCID: PMC5051646
PMID: 27493202
url
https://doi.org/10.1242/bio.020461View
Published (Version of record) Open Access

Abstract

RPGR (retinitis pigmentosa GTPase regulator) is a ciliary protein associated with several forms of inherited retinal degenerative diseases. PDE6D is a ubiquitously expressed prenyl-binding protein and involved in ciliary targeting of prenylated proteins. The current working model for the RPGR function depicts that RPGR acts as a scaffold protein to recruit cargo-loaded PDE6D to primary cilia. Here, we present evidence demonstrating an alternative relationship between RPGR and PDE6D, in which RPGR is a cargo of PDE6D for ciliary targeting. We found that the constitutive isoform of RPGR, which is prenylated, requires prenylation for its ciliary localization. We also found that there are at least two independent ciliary targeting signals in RPGR: one within the N-terminal region that contains the RCC1-like domain and the other near the prenylation site at the C-terminus. Ablation of PDE6D blocked ciliary targeting of RPGR. Our study indicates that prenylated RPGR is one of the cargos of PDE6D for ciliary trafficking and provides insight into the mechanisms by which RPGR is targeted to cilia. Summary: RPGR is a ciliary protein that functions as a scaffold to recruit cargo-loaded PDE6D to cilia. Our study shows that RPGR is also a cargo of PDE6D.
 Prenylation Retinitis pigmentosa Primary cilia Trafficking Photoreceptor degeneration

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