A multivalent PDZ-domain protein assembles signalling complexes in a G-protein-coupled cascade

Tsunoda, Susan; Sierralta, Jimena; Sun, Yanan; Bodner, Ruth; Suzuki, Emiko; Becker, Ann; Socolich, Michael; Zuker, Charles S.

doi:10.1038/40805

Cited by 600 publications

(579 citation statements)

References 3 publications

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“…As described above, the core-binding proteins depend on INAD for localization in the rhabdomeres and for protein stability [173,198]. It also seems plausible that nucleation of an array of signaling proteins in a complex would promote rapid signaling.…”

Section: The Signalplexmentioning

confidence: 98%

“…The "core complex" [195] consists of INAD and three proteins that bind directly to INAD: TRP, INAC (PKC) and NORPA (PLC) [173,196,197]. Each of the three target proteins that are included in the core complex is expressed at similar levels [196] and may always be present in the complex as they depend on INAD for normal localization in the rhabdomeres and protein stability [173,198].…”

Section: The Signalplexmentioning

confidence: 99%

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Phototransduction and retinal degeneration in Drosophila

Wang

Montell

2007

Pflugers Arch - Eur J Physiol

261

303

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Drosophila visual transduction is the fastest known G-protein-coupled signaling cascade and has therefore served as a genetically tractable animal model for characterizing rapid responses to sensory stimulation. Mutations in over 30 genes have been identified, which affect activation, adaptation, or termination of the photoresponse. Based on analyses of these genes, a model for phototransduction has emerged, which involves phosphoinoside signaling and culminates with opening of the TRP and TRPL cation channels. Many of the proteins that function in phototransduction are coupled to the PDZ containing scaffold protein INAD and form a supramolecular signaling complex, the signalplex. Arrestin, TRPL, and Gα q undergo dynamic light-dependent trafficking, and these movements function in long-term adaptation. Other proteins play important roles either in the formation or maturation of rhodopsin, or in regeneration of phosphatidylinositol 4,5-bisphosphate (PIP 2 ), which is required for the photoresponse. Mutation of nearly any gene that functions in the photoresponse results in retinal degeneration. The underlying bases of photoreceptor cell death are diverse and involve mechanisms such as excessive endocytosis of rhodopsin due to stable rhodopsin/arrestin complexes and abnormally low or high levels of Ca 2+ . Drosophila visual transduction appears to have particular relevance to the cascade in the intrinsically photosensitive retinal ganglion cells in mammals, as the photoresponse in these latter cells appears to operate through a remarkably similar mechanism.

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Section: The Signalplexmentioning

confidence: 98%

Section: The Signalplexmentioning

confidence: 99%

Phototransduction and retinal degeneration in Drosophila

Wang

Montell

2007

Pflugers Arch - Eur J Physiol

261

303

View full text Add to dashboard Cite

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“…[13][14][15][16][17][18][19] Multiprotein signaling complexes constitute the principle signaling units of neuronal synapses, [20,21] immune synapses, [13,22,23] focal adhesions, [24] and bacterial chemoreceptor arrays ( Figure 1). [25,26] These ensembles are composed of receptors, signaling proteins, adapter proteins, and cytoskeletal components.…”

Section: Signaling Complexesmentioning

confidence: 99%

Synthetic Multivalent Ligands as Probes of Signal Transduction

2006

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Cell surface receptors acquire information from the extracellular environment and coordinate intracellular responses. Evidence from biochemical and structural studies indicates that many receptors do not operate as individual entities, but rather as part of higher-order complexes (e.g. dimers and oligomers). Coupling the functions of multiple receptors may endow signaling pathways with the sensitivity and malleability required to govern cellular responses. Moreover, multireceptor signaling complexes may provide a means of spatially segregating otherwise degenerate signaling cascades. Despite the proposed importance of receptor-receptor processes in cellular signaling, questions concerning the mechanisms, extent, and consequences of receptor co-localization and interreceptor communication remain unanswered.Chemical synthesis can provide a variety of compounds with which to address the role of receptor assembly in signal transduction. The focus of this review is one such approach -the use of synthetic multivalent ligands to characterize receptor function. Multivalent ligands can be generated that possess a variety of sizes, shapes, valencies, orientations, and densities of binding elements. Their unique architectures imbue multivalent ligands with the ability to access binding modes not available to monovalent compounds. Multivalent ligands, therefore, are capable of illuminating aspects of inter-receptor processes that are not readily probed using conventional approaches. We suggest that, as focus shifts from investigations of the function of individual proteins and toward the analysis of multi-receptor signaling complexes, multivalent ligands will become even more valuable tools with which to ask sophisticated mechanistic questions. Further, multivalent ligands may provide new opportunities for manipulating receptor systems for the deconvolution of pathways, diagnosis, and, ultimately, the treatment of disease.

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“…In the case of the L/R asymmetric ASE and AWC neurons, this feat is achieved simply by segregating responsiveness to different chemicals to the left or the right neuron [98,99]. However, for cues sensed by both left and right neurons, one mechanism by which the signal transduction pathways could be insulated is via segregation of individual signaling pathways into signaling microdomains [142,[148][149][150][151]. It is also possible that while the core components of the signal transduction pathways are shared, additional molecules act in an odorant pathwayspecific manner [140], allowing the neuron to discriminate between multiple chemical cues.…”

Section: The Molecules For Taste and Smellmentioning

confidence: 99%

Generation and modulation of chemosensory behaviors in C. elegans

Sengupta

2007

Pflugers Arch - Eur J Physiol

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C. elegans recognizes and discriminates among hundreds of chemical cues using a relatively compact chemosensory nervous system. Chemosensory behaviors are also modulated by prior experience and contextual cues. Because of the facile genetics and genomics possible in this organism, C. elegans provides an excellent system in which to explore the generation of chemosensory behaviors from the level of a single gene to the motor output. This review summarizes the current knowledge on the molecular and neuronal substrates of chemosensory behaviors and chemosensory behavioral plasticity in C. elegans.

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A multivalent PDZ-domain protein assembles signalling complexes in a G-protein-coupled cascade

Cited by 600 publications

References 3 publications

Phototransduction and retinal degeneration in Drosophila

Phototransduction and retinal degeneration in Drosophila

Synthetic Multivalent Ligands as Probes of Signal Transduction

Generation and modulation of chemosensory behaviors in C. elegans

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