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Termination of phototransduction requires binding of the NINAC myosin III and the PDZ protein INAD

Nature Neuroscience volume 2, pages 447–453 (1999)Cite this article

Abstract

Many of the proteins that are critical for Drosophila phototransduction assemble into a signaling complex, signalplex, through association with the PDZ-domain protein INAD. Some of these proteins depend on INAD for proper subcellular localization to the phototransducing organelle, the rhabdomere, making it difficult to assess any physiological function of this signaling complex independent of localization. Here we demonstrated that INAD bound directly to the NINAC myosin III, yet the subcellular localization of NINAC was normal in inaD mutants. Nevertheless, the INAD binding site was sufficient to target a heterologous protein to the rhabdomeres. Disruption of the NINAC/INAD interaction delayed termination of the photoreceptor response. Thus one role of this signaling complex is in rapid deactivation of the photoresponse.

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Figure 1: NINAC and INAD interacted in column-binding assays.
Figure 2: Identification of interaction domains of NINAC and INAD using the yeast two-hybrid system.
Figure 3: NINAC and INAD interacted in vivo.
Figure 4: Rhabdomere-specific localization of NINAC did not require that NINAC interacted with INAD.
Figure 5: The INAD-binding site of NINAC was sufficient to target β-galactosidase to the rhabdomeres.
Figure 6: P[ninaCI1501E] flies showed defective termination of the photoreceptor response.

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Acknowledgements

We thank W.L. Pak and L.L.R. Strong for instruction in the intracellular recordings, D.R. Hyde for antibodies to Gqα, C.S. Zuker for inaD1 flies, K.M.C. Sullivan for critiquing the manuscript and S. Morgan for technical assistance. P.D.W. was a HHMI Predoctoral Fellow. This investigation was supported by a grant from the National Eye Institute to C.M. (EY08117).

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  1. Paul D. Wes

    Present address: Department of Anatomy, University of California, 513 Parnassus Ave., San Francisco, California, 94143, USA

  2. The first two authors contributed equally to this work.

Authors and Affiliations

  1. Departments of Biological Chemistry and Neuroscience, The Johns Hopkins University School of Medicine, 725 N. Wolfe St., Baltimore, 21205, Maryland, USA

    Paul D. Wes, Xian-Zhong Shawn Xu, Hong-Sheng Li, Fred Chien, Stephen K. Doberstein & Craig Montell

  2. Exelixis Pharmaceuticals, Inc., 260 Littlefield Avenue, South San Francisco, California, 94080, USA

    Stephen K. Doberstein

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Wes, P., Xu, XZ., Li, HS. et al. Termination of phototransduction requires binding of the NINAC myosin III and the PDZ protein INAD. Nat Neurosci 2, 447–453 (1999). https://doi.org/10.1038/8116

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