Ceramide kinase regulates phospholipase C and phosphatidylinositol 4, 5, bisphosphate in phototransduction

Phosphoinositide-specific phospholipase C (PLC) is a central effector for many biological responses regulated by G-protein-coupled receptors including Drosophila phototransduction where light sensitive channels are activated downstream of NORPA, a PLCβ homolog. Here we show that the sphingolipid bio...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2009-11, Vol.106 (47), p.20063-20068
Main Authors: Dasgupta, Ujjaini, Bamba, Takeshi, Chiantia, Salvatore, Karim, Pusha, Tayoun, Ahmad N. Abou, Yonamine, Ikuko, Rawat, Satinder S, Rao, Raghavendra Pralhada, Nagashima, Kunio, Fukusaki, Eiichiro, Puri, Vishwajeet, Dolph, Patrick J, Schwille, Petra, Acharya, Jairaj K, Acharya, Usha
Format: Article
Language:English
Subjects:
Animals
Antibodies
Biological Sciences
Cell membranes
Ceramides
Ceramides - metabolism
Correlation analysis
Drosophila
Drosophila melanogaster - physiology
Drosophila Proteins - genetics
Drosophila Proteins - metabolism
Electroretinography
Fluorescence
Gene expression regulation
Homeostasis
Insects
Intracellular Membranes - chemistry
Intracellular Membranes - metabolism
Light
Light Signal Transduction - physiology
Lipids
Membranes
Mutation
Phosphatidylinositol 4,5-Diphosphate - metabolism
Phosphatidylinositols
Phospholipase C beta - genetics
Phospholipase C beta - metabolism
Phosphotransferases (Alcohol Group Acceptor) - genetics
Phosphotransferases (Alcohol Group Acceptor) - metabolism
Photoreceptor Cells, Invertebrate - physiology
Photoreceptor Cells, Invertebrate - ultrastructure
Photoreceptors
Phototransduction
Proteins
Recombinant Fusion Proteins - genetics
Recombinant Fusion Proteins - metabolism
Signal transduction
Signal Transduction - physiology
Sphingolipids
Type C Phospholipases - genetics
Type C Phospholipases - metabolism
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Summary:Phosphoinositide-specific phospholipase C (PLC) is a central effector for many biological responses regulated by G-protein-coupled receptors including Drosophila phototransduction where light sensitive channels are activated downstream of NORPA, a PLCβ homolog. Here we show that the sphingolipid biosynthetic enzyme, ceramide kinase, is a novel regulator of PLC signaling and photoreceptor homeostasis. A mutation in ceramide kinase specifically leads to proteolysis of NORPA, consequent loss of PLC activity, and failure in light signal transduction. The mutant photoreceptors also undergo activity-dependent degeneration. Furthermore, we show that a significant increase in ceramide, resulting from lack of ceramide kinase, perturbs the membrane microenvironment of phosphatidylinositol 4, 5, bisphosphate (PIP₂), altering its distribution. Fluorescence image correlation spectroscopic studies on model membranes suggest that an increase in ceramide decreases clustering of PIP₂ and its partitioning into ordered membrane domains. Thus ceramide kinase-mediated maintenance of ceramide level is important for the local regulation of PIP₂ and PLC during phototransduction.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0911028106