Cell Non-autonomous Function of Ceramidase in Photoreceptor Homeostasis

Neutral Ceramidase, a key enzyme of sphingolipid metabolism, hydrolyzes ceramide to sphingosine. These sphingolipids are critical structural components of cell membranes and act as second messengers in diverse signal transduction cascades. Here, we have isolated and characterized functional null mutants of Drosophila Ceramidase. We show that secreted Ceramidase functions in a cell non-autonomous manner to maintain photoreceptor homeostasis. In the absence of Ceramidase, photoreceptors degenerate in a light-dependent manner, are defective in normal endocytic turnover of Rhodopsin, and do not respond to light stimulus. Consistent with a cell non-autonomous function, our studies show that over expression of Ceramidase in a tissue distant from the photoreceptors can suppress photoreceptor degeneration in an Arrestin mutant and facilitate membrane turnover in a Rhodopsin null mutant. Furthermore, our results show that secreted CDase is internalized and localizes to endosomes. Our findings are the first to establish a role for a secreted sphingolipid enzyme in the regulation of photoreceptor structure and function.