Ceramide kinase regulates phospholipase C and phosphatidylinositol 4, 5, bisphosphate in phototransduction
Authors
Dasgupta, UjjainiBamba, 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
Document Type
Journal ArticlePublication Date
2009-11-07Keywords
AnimalsCeramides
Drosophila Proteins
Drosophila melanogaster
Electroretinography
Homeostasis
Intracellular Membranes
Light
Light Signal Transduction
Mutation
Phosphatidylinositol 4,5-Diphosphate
Phospholipase C beta
Phosphotransferases (Alcohol Group Acceptor)
Photoreceptor Cells, Invertebrate
Recombinant Fusion Proteins
Signal Transduction
Type C Phospholipases
Genetics and Genomics
Metadata
Show full item recordAbstract
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 PLCbeta 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 (PIP(2)), altering its distribution. Fluorescence image correlation spectroscopic studies on model membranes suggest that an increase in ceramide decreases clustering of PIP(2) and its partitioning into ordered membrane domains. Thus ceramide kinase-mediated maintenance of ceramide level is important for the local regulation of PIP(2) and PLC during phototransduction.Source
Proc Natl Acad Sci U S A. 2009 Nov 24;106(47):20063-8. Epub 2009 Nov 5. Link to article on publisher's siteDOI
10.1073/pnas.0911028106Permanent Link to this Item
http://hdl.handle.net/20.500.14038/44091PubMed ID
19892737Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1073/pnas.0911028106