Dawn, diacylglycerol, calcium, and protein kinase C--the retinal wrecking crew. A signal transduction cascade for rhabdom shedding in the Limulus eye.
Vertebrate and invertebrate photoreceptors shed their photosensitive membrane on a daily basis. Although we have detailed knowledge of the morphology of the disc shedding and renewal process in vertebrate photoreceptors, and of the turnover of rhabdom in invertebrate photoreceptors, we know relatively little about the molecular mechanisms whereby these processes are triggered by light and/or by circadian efferent input to the retina. We have used the horseshoe crab, Limulus polyphemus, as a model system to unravel the molecular means by which the trigger light is communicated to the intracellular machinery responsible for the daily breakdown of the photosensitive membrane. Phorbol esters, potent and specific activators of protein kinase C (PKC), induce a robust burst of rhabdom shedding when injected subretinally into the compound lateral eye of Limulus. This occurs in the absence of the light trigger normally required to initiate shedding in the lateral eye at dawn, suggesting that PKC may play a role in the light triggering of rhabdom shedding. Diacylglycerol (DAG) analogs were also found to elicit rhabdom shedding in the lateral eye without a light trigger, but at uncharacteristically high concentrations. However, injecting inositol trisphosphate (InsP3) and DAG analog simultaneously results in a tenfold decrease in the concentration of DAG analog required to initiate a shedding event. Immunohistochemical screening for PKC in the lateral eye shows that two isozymes (PKC beta II and PKC zeta) are co-localized to the retinular cell rhabdom. Taken together, these data suggest that light triggers rhabdom shedding at dawn via a classical Ca(2+)-sensitive PKC, similar to PKC beta II, which is activated synergistically by the light-evoked production of DAG and InsP3.
Jinks
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RN
Institute for Sensory Research, Syracuse University, NY 13244-5290, USA.
White
R H
RH
Chamberlain
S C
SC
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002417:Cattle; D004075:Diglycerides / Q000494:pharmacology*; D005123:Eye / Q000378:metabolism; D019084:Fluorescent Antibody Technique, Indirect; D006737:Horseshoe Crabs / Q000378:metabolism*; D006801:Humans; D007295:Inositol Phosphates / Q000494:pharmacology; D007527:Isoenzymes / Q000378:metabolism*; D008027:Light; D008297:Male; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D004075:Diglycerides; D007295:Inositol Phosphates; D007527:Isoenzymes; C092449:inositol 1,2,3-trisphosphate; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium