A research group that previously showed that overexpression of ceramidase (CDase) in Drosophila photoreceptors suppressed retinal degeneration in response to certain mutations has now made the intriguing discovery that CDase regulation of photoreceptor function is cell nonautonomous. CDases, which convert ceramide to sphingosine, play a key role in metabolism of the sphingolipids, a lipid family that comprises not only structural components of cell membranes but also signaling molecules. Acharya et al. created flies in which almost the entire eye was homozygous for a null mutation of CDase, whereas other regions were CDase heterozygous. Ultrastructural analysis revealed that the photoreceptors of the mosaic flies were structurally normal; furthermore, immunocytochemical analysis of eye discs and Western blot analysis of retinal extracts revealed CDase protein. Overexpression of CDase in the fat body or in mushroom body neurons (tissues distinct from the retina) rescued photoreceptor degeneration in arrestin mutants and stimulated rhabdomeric membrane turnover in rhodopsin-null mutants. Viable functional CDase-null mutants experienced light-dependent photoreceptor degeneration; interactions between rhodopsin and arrestins in the CDase-null mutant flies were abnormal, and the photoreceptors of dark-raised mutant flies failed to respond to light. Retinal extracts of CDase-null mutants in which CDase was overexpressed in the fat body showed CDase activity, and eye discs in these flies exhibited CDase immunoreactivity. Experiments with cultured Drosophila Schneider cells revealed that extracellular CDase hydrolyzed ceramide at the cell surface and was internalized to localize to endosomes. Thus, the authors conclude that CDase acts in a cell-nonautonomous manner to regulate Drosophila photoreceptor function and survival. Dolph discusses this research as well as research by Wang et al. implicating a SOCS box protein, which the authors named STOPS (slow termination of phototransduction), in Drosophila phototransduction.
J. K. Acharya, U. Dasgupta, S. S. Rawat, C. Yuan, P. D. Sanxaridis, I. Yonamine, P. Karim, K. Nagashima, M. H. Brodsky, S. Tsunoda, U. Acharya, Cell-nonautonomous function of ceramidase in photoreceptor homeostasis. Neuron 57, 69-79 (2008). [PubMed]
T. Wang, X. Wang, Q. Xie, C. Montell, The SOCS box protein STOPS is required for phototransduction through its effects on phospholipase C. Neuron 57, 56-68 (2008). [PubMed]
P. Dolph, New insights into Drosophila vision. Neuron 57, 1-2 (2008). [PubMed]