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

Nature volume 388, pages 243–249 (1997)Cite this article

Abstract

How are signalling molecules organized into different pathways within the same cell? In Drosophila, the inaD gene encodes a protein consisting of five PDZ domains which serves as a scaffold to assemble different components of the phototransduction cascade, including the principal light-activated ion channels, the effector phospholipase C-β and protein kinase C. Null inaD mutants have a dramatically reorganized subcellular distribution of signalling molecules, and a total loss of transduction complexes. Also, mutants defective in a single PDZ domain produce signalling complexes that lack the target protein and display corresponding defects in their physiology. A picture emerges of a highly organized unit of signalling, a ‘transducisome’, with PDZ domains functioning as key elements in the organization of transduction complexes in vivo.

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Figure 1: InaD is composed of five distinct PDZ domains.
Figure 2: 2 InaD forms a complex with PLC/PKC/TRP.
Figure 3: 3 TRP, eye-PKC and PLC are mislocalized in inaD1 null mutant photoreceptors.
Figure 4: Photoresponses of inaD1 and inaD2.
Figure 5: Transduction proteins that fail to associate with InaD become unstable.
Figure 6: inaD215 and inaD2 mutants show specific mislocalization of TRP and PLC.
Figure 7: Photoresponses of inaD215.

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Acknowledgements

We thank B. Niemeyer for advice, initial observations and discussions; D. Schultz for help with the yeast two-hybrid system; E. Koundakjian and D. Cowan for help with the F3 screen; and R.MacKinnon and members of the Zuker laboratory for discussions. S.T. is a fellow of the American Cancer Society; J. S. is supported by the Pew Latin American Scholars Program; R.B. was supported by a Markey predoctoral training grant; and C.S.Z. is an investigator of the Howard Hughes Medical Institute.

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  1. Howard Hughes Medical Institute and Departments of Biology and Neurosciences, University of California at San Diego, La Jolla, 92093-0649, California, USA

    Susan Tsunoda, Jimena Sierralta, Yumei Sun, Ruth Bodner, Ann Becker, Michael Socolich & Charles S. Zuker

  2. *The Insitute of Medical Science, The University of Tokyo, Japan

    Emiko Suzuki

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  1. Susan Tsunoda
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Correspondence to Charles S. Zuker.

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Tsunoda, S., Sierralta, J., Sun, Y. et al. A multivalent PDZ-domain protein assembles signalling complexes in a G-protein-coupled cascade. Nature 388, 243–249 (1997). https://doi.org/10.1038/40805

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