title: A novel Usher protein network at the periciliary reloading point between molecular transport machineries in vertebrate photoreceptor cells.
abstract: The human Usher syndrome (USH) is the most frequent cause of combined deaf-blindness. USH is genetically heterogeneous with at least 12 chromosomal loci assigned to three clinical types, USH1-3. Although these USH types exhibit similar phenotypes in human, the corresponding gene products belong to very different protein classes and families. The scaffold protein harmonin (USH1C) was shown to integrate all identified USH1 and USH2 molecules into protein networks. Here, we analyzed a protein network organized in the absence of harmonin by the scaffold proteins SANS (USH1G) and whirlin (USH2D). Immunoelectron microscopic analyses disclosed the colocalization of all network components in the apical inner segment collar and the ciliary apparatus of mammalian photoreceptor cells. In this complex, whirlin and SANS directly interact. Furthermore, SANS provides a linkage to the microtubule transport machinery, whereas whirlin may anchor USH2A isoform b and VLGR1b (very large G-protein coupled receptor 1b) via binding to their cytodomains at specific membrane domains. The long ectodomains of both transmembrane proteins extend into the gap between the adjacent membranes of the connecting cilium and the apical inner segment. Analyses of Vlgr1/del7TM mice revealed the ectodomain of VLGR1b as a component of fibrous links present in this gap. Comparative analyses of mouse and Xenopus photoreceptors demonstrated that this USH protein network is also part of the periciliary ridge complex in Xenopus. Since this structural specialization in amphibian photoreceptor cells defines a specialized membrane domain for docking and fusion of transport vesicles, we suggest a prominent role of the USH proteins in cargo shipment.
authors: Department of Cell and Matrix Biology, Institute of Zoology, Johannes Gutenberg University of Mainz, 55099 Mainz, Germany.
authors: Tina
authors: T
authors: Maerker
authors: Erwin
authors: E
authors: van Wijk
authors: Nora
authors: N
authors: Overlack
authors: Ferry F J
authors: FF
authors: Kersten
authors: Joann
authors: J
authors: McGee
authors: Tobias
authors: T
authors: Goldmann
authors: Elisabeth
authors: E
authors: Sehn
authors: Ronald
authors: R
authors: Roepman
authors: Edward J
authors: EJ
authors: Walsh
authors: Hannie
authors: H
authors: Kremer
authors: Uwe
authors: U
authors: Wolfrum
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000818:Animals; D019556:COS Cells; D018797:Cell Cycle Proteins; D002522:Chlorocebus aethiops; D003598:Cytoskeletal Proteins; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016253:Microscopy, Immunoelectron; D008954:Models, Biological; D041681:NIH 3T3 Cells; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D020419:Photoreceptor Cells, Vertebrate / Q000378:metabolism* / Q000648:ultrastructure; D025941:Protein Interaction Mapping; D043562:Receptors, G-Protein-Coupled / Q000172:deficiency / Q000235:genetics; D013347:Subcellular Fractions / Q000378:metabolism; D014162:Transfection; D052245:Usher Syndromes / Q000145:classification / Q000235:genetics* / Q000378:metabolism*; D014981:Xenopus / Q000235:genetics / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D016326:Extracellular Matrix Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D043562:Receptors, G-Protein-Coupled; C485949:Adgrv1 protein, mouse; C477451:Sans protein, mouse; C118970:USH1C protein, human; C477452:USH1G protein, human; C112735:USH2A protein, human; C477219:WHRN protein, human