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
