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Mol Vis. 2010 Jul 17;16:1373-81.

Interaction of ciliary disease protein retinitis pigmentosa GTPase regulator with nephronophthisis-associated proteins in mammalian retinas.

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Department of Ophthalmology and Visual Sciences, Howard Hughes Medical Institute, University of Michigan, Ann Arbor, MI, USA.



Retinitis pigmentosa GTPase regulator (RPGR) is a cilia-centrosomal protein that frequently mutates in X-linked retinal degeneration and associated disorders. RPGR interacts with multiple ciliary proteins in the retina. Perturbations in the assembly of RPGR complexes are associated with retinal degeneration. This study was undertaken to delineate the composition and dissection of RPGR complexes in mammalian retinas.


Immunoprecipitation of RPGR from ciliary fraction of bovine retina was performed, followed by mass spectrometry analysis. The glutathione S-transferase pull-down assay was performed to validate the interaction. Immunodepletion experiments were performed to dissect the partitioning of RPGR in different protein complexes in mammalian retinas.


We found that RPGR associates with a ciliary protein nephrocystin-4 (nephroretinin; NPHP4) that is mutated in nephronophthisis (NPH) and RP (Senior-Løken syndrome). This association is abolished in the Rpgr-knockout mouse retina. The RCC1-like domain of RPGR interacts with the N-terminal 316 amino acids of NPHP4. In the retina, RPGR also associates with NPHP1, an NPHP4-interacting protein; RPGR interacts directly with amino acids 243-586 of NPHP1. We further show that, in the retina, RPGR associates with and is partitioned in at least two different complexes with NPHP-associated proteins, (i) NPHP1, NPHP2, and NPHP5, and (ii) NPHP4, NPHP6, and NPHP8.


RPGR may regulate some complexes with NPHP proteins in the mammalian retina. The disruption of these complexes may contribute to the pathogenesis of retinal degeneration in X-linked RP and associated ciliary diseases.

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