Coordination of an array of signaling proteins through homo- and heteromeric interactions between PDZ domains and target proteins

TitleCoordination of an array of signaling proteins through homo- and heteromeric interactions between PDZ domains and target proteins
Publication TypeJournal Article
Year of Publication1998
AuthorsXu XZ, Choudhury A, Li X, Montell C
JournalJ Cell Biol
Volume142
Pagination545-55
Date Published1998 Jul 27
ISSN0021-9525
KeywordsAnimals, Binding Sites, Calmodulin, Calmodulin-Binding Proteins, Drosophila, Drosophila Proteins, Eye Proteins, Insect Proteins, Ion Channels, Macromolecular Substances, Membrane Proteins, Mutagenesis, Site-Directed, Photoreceptor Cells, Invertebrate, Protein Binding, Protein Kinase C, Rhodopsin, Rod Opsins, Signal Transduction, Transient Receptor Potential Channels, Vision, Ocular
Abstract

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.

Alternate JournalJ. Cell Biol.
PubMed ID9679151
PubMed Central IDPMC2133053
Grant ListEY08117 / EY / NEI NIH HHS / United States