Coordination of an array of signaling proteins through homo- and heteromeric interactions between PDZ domains and target proteins.
The rapid activation and feedback regulation of many G protein signaling cascades raises the possibility that the critical signaling proteins may be tightly coupled. Previous studies show that the PDZ domain containing protein INAD, which functions in Drosophila vision, coordinates a signaling complex by binding directly to the light-sensitive ion channel, TRP, and to phospholipase C (PLC). The INAD signaling complex also includes rhodopsin, protein kinase C (PKC), and calmodulin, though it is not known whether these proteins bind to INAD. In the current work, we show that rhodopsin, calmodulin, and PKC associate with the signaling complex by direct binding to INAD. We also found that a second ion channel, TRPL, bound to INAD. Thus, most of the proteins involved directly in phototransduction appear to bind to INAD. Furthermore, we found that INAD formed homopolymers and the homomultimerization occurred through two PDZ domains. Thus, we propose that the INAD supramolecular complex is a higher order signaling web consisting of an extended network of INAD molecules through which a G protein-coupled cascade is tethered.
Department of Biological Chemistry and Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
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Choudhury
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Montell
D000818:Animals; D001665:Binding Sites / Q000235:genetics; D002147:Calmodulin / Q000378:metabolism; D002148:Calmodulin-Binding Proteins / Q000378:metabolism; D004330:Drosophila / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D029721:Drosophila Proteins; D005136:Eye Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D019476:Insect Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D007473:Ion Channels / Q000378:metabolism; D046911:Macromolecular Substances; D008565:Membrane Proteins / Q000378:metabolism; D016297:Mutagenesis, Site-Directed; D017956:Photoreceptor Cells, Invertebrate / Q000378:metabolism; D011485:Protein Binding; D011493:Protein Kinase C / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012243:Rhodopsin / Q000378:metabolism; D017299:Rod Opsins / Q000378:metabolism; D015398:Signal Transduction; D050051:Transient Receptor Potential Channels; D014785:Vision, Ocular / Q000502:physiology
D002147:Calmodulin; D002148:Calmodulin-Binding Proteins; D029721:Drosophila Proteins; D005136:Eye Proteins; D019476:Insect Proteins; D007473:Ion Channels; D046911:Macromolecular Substances; D008565:Membrane Proteins; D017299:Rod Opsins; D050051:Transient Receptor Potential Channels; C092747:cno protein, Drosophila; C091568:inaD protein, Drosophila; C074192:trpl protein, Drosophila; D012243:Rhodopsin; D011493:Protein Kinase C