Article

Cell-nonautonomous function of ceramidase in photoreceptor homeostasis.

Laboratory of Cell and Developmental Signaling, National Cancer Institute, Frederick, MD 21702, USA.
Neuron (impact factor: 14.74). 02/2008; 57(1):69-79. DOI:10.1016/j.neuron.2007.10.041
Source: PubMed

ABSTRACT 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-nonautonomous 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-nonautonomous function, overexpression of ceramidase in tissues distant from photoreceptors suppresses photoreceptor degeneration in an arrestin mutant and facilitates membrane turnover in a rhodopsin null mutant. Furthermore, our results show that secreted ceramidase is internalized and localizes to endosomes. Our findings establish a role for a secreted sphingolipid enzyme in the regulation of photoreceptor structure and function.

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Keywords

arrestin mutant
 
cell membranes
 
cell-nonautonomous function
 
Drosophila ceramidase
 
facilitates membrane turnover
 
functional null mutants
 
key enzyme
 
Neutral ceramidase
 
normal endocytic turnover
 
photoreceptor homeostasis
 
photoreceptor structure
 
photoreceptors degenerate
 
photoreceptors suppresses photoreceptor degeneration
 
rhodopsin null mutant
 
second messengers
 
secreted ceramidase
 
secreted ceramidase functions
 
secreted sphingolipid enzyme
 
sphingolipid metabolism
 
tissues distant