title: Structural and functional protein network analyses predict novel signaling functions for rhodopsin.
abstract: Orchestration of signaling, photoreceptor structural integrity, and maintenance needed for mammalian vision remain enigmatic. By integrating three proteomic data sets, literature mining, computational analyses, and structural information, we have generated a multiscale signal transduction network linked to the visual G protein-coupled receptor (GPCR) rhodopsin, the major protein component of rod outer segments. This network was complemented by domain decomposition of protein-protein interactions and then qualified for mutually exclusive or mutually compatible interactions and ternary complex formation using structural data. The resulting information not only offers a comprehensive view of signal transduction induced by this GPCR but also suggests novel signaling routes to cytoskeleton dynamics and vesicular trafficking, predicting an important level of regulation through small GTPases. Further, it demonstrates a specific disease susceptibility of the core visual pathway due to the uniqueness of its components present mainly in the eye. As a comprehensive multiscale network, it can serve as a basis to elucidate the physiological principles of photoreceptor function, identify potential disease-associated genes and proteins, and guide the development of therapies that target specific branches of the signaling pathway.
authors: EMBL/CRG Systems Biology Research Unit, Centre for Genomic Regulation, UPF, Barcelona, Spain.
authors: Christina
authors: C
authors: Kiel
authors: Andreas
authors: A
authors: Vogt
authors: Anne
authors: A
authors: Campagna
authors: Andrew
authors: A
authors: Chatr-aryamontri
authors: Magdalena
authors: M
authors: Swiatek-de Lange
authors: Monika
authors: M
authors: Beer
authors: Sylvia
authors: S
authors: Bolz
authors: Andreas F
authors: AF
authors: Mack
authors: Norbert
authors: N
authors: Kinkl
authors: Gianni
authors: G
authors: Cesareni
authors: Luis
authors: L
authors: Serrano
authors: Marius
authors: M
authors: Ueffing
mesh_terms: D008841:Actin Cytoskeleton; D000818:Animals; D002450:Cell Communication; D055537:Light Signal Transduction; D060066:Protein Interaction Maps; D020543:Proteome; D012243:Rhodopsin / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D012374:Rod Cell Outer Segment / Q000378:metabolism*; D013552:Swine; D014785:Vision, Ocular; D014795:Visual Pathways
chemical_list: D020543:Proteome; D012243:Rhodopsin