Cell-nonautonomous function of ceramidase in photoreceptor homeostasis
Acharya, Jairaj K. ; Dasgupta, Ujjaini ; Rawat, Satinder S. ; Yuan, Changqing ; Sanxaridis, Parthena D. ; Yonamine, Ikuko ; Karim, Pusha ; Nagashima, Kunio ; Brodsky, Michael H. ; Tsunoda, Susan ... show 1 more
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Student Authors
Faculty Advisor
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UMass Chan Affiliations
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Keywords
Animals
Animals, Genetically Modified
Apoptosis
Arrestin
Ceramidases
Drosophila
Drosophila Proteins
Electroretinography
Embryo, Nonmammalian
Eye
Fat Body
Gene Expression Regulation, Developmental
Homeostasis
Membrane Potentials
Mutation
Photic Stimulation
Photoreceptor Cells, Invertebrate
Protein Binding
Retinal Degeneration
Rhodopsin
Sphingosine
Genetics and Genomics
Subject Area
Embargo Expiration Date
Link to Full Text
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.
Source
Neuron. 2008 Jan 10;57(1):69-79. Link to article on publisher's site