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Prenylated retinal ciliopathy protein RPGR interacts with PDE6B,

Regulates ciliary localization of Joubert syndrome-associated protein INPP5E

Kollu N. Rao, Wei Zhang, Linjing Li, Manisha Anand, and Hemant Khanna, Human Molecular Genetics | Vol 25, Issue 20 | pgs. 4533 - 4545 | 15 Oct 2016 |


Ciliary trafficking defects underlie the pathogenesis of severe human ciliopathies, including Joubert Syndrome (JBTS), Bardet-Biedl Syndrome, and some forms of retinitis pigmentosa (RP). Mutations in the ciliary protein RPGR (retinitis pigmentosa GTPase regulator) are common causes of RP-associated photoreceptor degeneration worldwide. While previous work has suggested that the localization of RPGR to cilia is critical to its functions, the mechanism by which RPGR and its associated cargo are trafficked to the cilia is unclear. Using proteomic and biochemical approaches, we show that RPGR interacts with two JBTS-associated ciliary proteins: PDE6B (delta subunit of phosphodiesterase; a prenyl-binding protein) and INPP5E (inositol polyphosphate-5-phosphatase 5E). We find that PDE6B binds selectively to the C-terminus of RPGR and that this interaction is critical for RPGR’s localization to cilia.


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