Protein networks and complexes in photoreceptor cilia.

Vertebrate photoreceptor cells are ciliated sensory cells specialized for single photon detection. The photoreceptor outer segment corresponds to the ciliary shaft of a prototypic cilium. In the outer segment compartment, the ciliary membrane is highly modified into membranous disks which are enveloped by the plasma membrane in rod cells. At these outer segment disks, the visual transduction cascade--a prototypical G-protein coupled receptor transduction pathway is arranged. The light sensitive outer segments are linked by the socalled connecting cilium with the inner segment, the photoreceptor compartment which contains all organelles necessary for cell metabolism. The connecting cilium correlates with the transition zone, the short junction between the basal body and the axoneme of a prototypic cilium. The connecting cilium and the calycal processes, including the periciliary ridge complex, as well as the basal body complex are in close functional association with each other. In the latter ciliary compartments, the export and import from/into the outer segment of the photoreceptor cell are controlled and regulated. In all subciliary compartments, proteins are arranged in functional multiprotein complexes. In the outer segment, signaling components are arranged into complexes which provide specificity and speed for the signaling and serve in adaptation. Centrin-G-protein complexes may regulate the light driven translocation of the visual G-protein transducin through the connecting cilium. Intraflagellar transport (IFT) complexes may serve in intersegmental exchange of molecules. The import/export of molecules is thought to be regulated by proteins arranged in networks at the basal body complex. Proteins of the interactome related to the human Usher syndrome are localized in the connecting cilium and may participate in the ciliary transport, but are also arranged at interfaces between the inner segment and the connecting cilium where they probably control the cargo handover between the transport systems of the inner segment and these of the cilium. Furthermore, USH protein complexes may further provide mechanical stabilization to membrane specializations of the calycal processes and the connecting cilium. The protein complex in which the retinitis pigmentosa GTPase regulator (RPGR) participates in the ciliary compartments also plays a key role in the function and maintenance of photoreceptor cells. It further associates through the presumed scaffolding protein RPGRIP1 with the nephrocystin protein network. Although many of these proteins have been also found in prototypic cilia or primary cilia, the arrangements of the proteins in complexes can be specific for vertebrate photoreceptor cells. Defects of proteins in these complexes lead to photoreceptor cell death and retinal degeneration, underlying syndromic and non-syndromic blindness.