How do steps in the phototransduction cascade interact in photoreceptor maintenance and phototransduction? I first pursued this question because of the finding of a unique interaction of the norpA (no receptor potential) and rdgB (receptor degeneration) genes (Harris and Stark,1977, see Retinal degeneration and visual pigment...). As I started to study membrane turnover (see Photoreceptor maintenance...) I was fortunate to obtain a large freeze-fracture replica of norpA (Stark et al., 1989). Together with a substantial body of electron micrographs, as well as microspectrophotometric and electrophysiological data, I characterized norpA's structural anomalies (Stark and Sapp, 1989) and the light-dependency of norpA's improper maintenance [light-dependent retinal degeneration] (Zinkl et al., 1990). More recently, my laboratory collaborated with Randall Shortridge (State University of New York - Buffalo) and his students in examining the rescue of norpA mutants in transgenic Drosophila with various forms of the PLC gene inserted into the genome. My Ph.D. student, K. Shim (Ph.D., 1997), spearheaded my laboratory's efforts in showing that retinoid deprivation decreases PLC in rhabdomeres, but only indirectly by decreasing rhabdomere size (Shim et al., 2001). Dr. Shortridge's graduate students K. Miller [now K. M. Zavarella] (Miller, 1997) and S. Kim (Chen, 1997) (Ph.D.'s, 1997) produced transgenic Drosophila with alterations in their PLC, and D.-M. Chen, in my laboratory, showed the specific alterations in photoexcitation in these strains. This collaboration led to a further collaboration with Min Li and his coworkers at The Johns Hopkins University demonstrating the interaction of NORPA and INAD through PDZ domains in a clustered group of phototransduction proteins. Most recently, I collaborated with Margie LaLonde, an MD-PhD student in Michael Frohman's laboratory, on phospholipase D (PLD) and retinal degeneration in Drosophila.

The original paper on the rdgB - norpA interaction:

Harris, W.A. and Stark, W.S. Hereditary retinal degeneration in Drosophila melanogaster: A mutant defect associated with the phototransduction process. The Journal of General Physiology, 1977, 69, 261-291. PubMed

Later papers on Drosophila norpA:

Stark, W.S., Sapp, R., and Carlson, S.D. Photoreceptor maintenance and degeneration in the norpA (no receptor potential-A) mutant of Drosophila melanogaster. Journal of Neurogenetics, 1989, 5, 49-59. PubMed

Stark, W.S. and Sapp, R. Retinal degeneration and photoreceptor maintenance in Drosophila: rdgB and its interaction with outer mutants. In: Inherited and Environmentally Induced Retinal Degenerations: (ed: M.M.LaVail, R. E. Anderson and J. G. Hollyfield) New York: Alan R. Liss, Inc.1989. pp. 467-489 (Invited Chapter). PubMed

Zinkl, G., Maier, L., Studer, K., Sapp, R., Chen, D.-M., Stark, W. S. Microphotometric, ultrastructural and electrophysiological analyses of light dependent processes on visual receptors in white-eyed wild-type and norpA (no receptor potential) mutant Drosophila. Visual Neuroscience, 1990, 5, 429-439. PubMed

McKay, R. R, Chen, D.-M., Miller, K., Kim, S., Stark, W. S., Shortridge, R. D. Phospholipase C rescues defect in norpA mutant of Drosophila melanogaster. Journal of Biological Chemistry, 1995, 270, 13271-13276. PubMed, Full paper on line, view PDF file

van Huizen, R., Miller, K., Chen, D.-M., Li, Y., Lai, Z.-C., Raab, R. W., Stark, W. S., Shortridge, R. D., Li, M. Two distantly positioned PDZ domains mediate multivalent INAD-phospholipase C interactions essential for the G protein-coupled signalling. EMBO Journal, 1998, 17, 2285-2297. PubMed, Full paper on line, View pdf file

Shim, K., Zavarella, K. M., Thomas, C. T., Shortridge, R. D., Stark, W. S. Evidence for indirect control of phospholipase C (PLC-b) by retinoids in Drosophila phototransduction. Molecular Vision, 2001; 7:216-221. PubMed, Full paper on line, View pdf file.

Kim, S., Chen, D.-M., Zavarella, K., Fourtner, C. F., Stark, W. S., Shortridge, R. D. Substitution of a non-retinal phospholipase C in Drosophila phototransduction. Insect Molecular Biology 12: 147-153, 2003. PubMed, Abstract on line

The PLD paper

Lalonde, M.M., Janssens, H., Rosenbaum, E., Choi, S.Y., Gergen, J. P., Colley, N.J., Stark, W.S., Frohman, M.A.. Regulation of phototransduction responsiveness and retinal degeneration by a phospholipase D-generated signaling lipid. J. Cell Biol. 169, 471-479, 2005. PubMed, Full paper on line, View pdf file.

A chapter putting this work into a broad perspective:

Stark, W. S. Comparative biology of receptor recovery by retinoid replacement in retinoid deprived flies and rodents. In Degenerative Retinal Diseases (eds. M. M. LaVail, J. G. Hollyfield, R. E. Anderson), New York, Plenum, 1997, 135-143.

An EM (Stark and Sapp, 1989)showing odd structures near rhabdomeres (R) in norpA, "zippers"(Z), cisterns (C) and an "island" or "peninsula" in the intraommatidial cavity (IOC); coated pits (arrows) and the multivesicular bodies (one in the island) are associated with turnover.

An electron micrograph showing normal T-bar synapses in norpA (from Stark et al., 1989); the evidence that these synapses work is discussed elsewhere (Zinkl et al., 1990)

This page was last updated on June 13, 2005

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