Ceramidase Expression Facilitates Membrane Turnover and Endocytosis of Rhodopsin in Photoreceptors

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 101; no. 7; pp. 1922 - 1926
• Main Authors: Acharya, Usha, Mowen, Michael Beth, Nagashima, Kunio, Acharya, Jairaj K., Lindsley, Dan L.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 17.02.2004; National Acad Sciences
• Subjects: Amidohydrolases - genetics; Amidohydrolases - metabolism; Animals; Animals, Genetically Modified; arrestin; Biological Sciences; Cell Membrane - genetics; Cell Membrane - metabolism; Cell membranes; Ceramidases; Ceramides; Darkness; Drosophila; Drosophila melanogaster - cytology; Drosophila melanogaster - enzymology; Drosophila melanogaster - genetics; Drosophila melanogaster - metabolism; Drosophila Proteins - genetics; Drosophila Proteins - metabolism; Endocytosis; Enzymes; Eye Proteins - genetics; Eye Proteins - metabolism; Genetics; Half lives; Half-Life; Insects; Ligands; Light; Membranes; Mutation; P branes; Photoreceptor Cells, Invertebrate - cytology; Photoreceptor Cells, Invertebrate - metabolism; Photoreceptor Cells, Invertebrate - radiation effects; Photoreceptors; Receptors; Receptors, G-Protein-Coupled - deficiency; Receptors, G-Protein-Coupled - metabolism; Retina; retinal; Retinal Degeneration - metabolism; Retinal Degeneration - pathology; Retinaldehyde; Rhodopsin - deficiency; Rhodopsin - genetics; Rhodopsin - metabolism; Shock heating; Sphingolipids
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0308693100

Transgenic expression of ceramidase suppresses retinal degeneration in Drosophila arrestin and phospholipase C mutants. Here, we show that expression of ceramidase facilitates the dissolution of incompletely formed and inappropriately located elements of rhabdomeric membranes in ninaEI17mutants lacking the G protein receptor Rh1 in R1-R6 photoreceptor cells. Ceramidase expression facilitates the endocytic turnover of Rh1. Although ceramidase expression aids the removal of internalized rhodopsin, it does not affect the turnover of Rh1 in photoreceptors maintained in dark, where Rh1 is not activated and thus has a slower turnover and a long half-life. Therefore, the phenotypic consequence of ceramidase expression in photoreceptors is caused by facilitation of endocytosis. This study provides mechanistic insight into the sphingolipid biosynthetic pathway-mediated modulation of endocytosis and suppression of retinal degeneration.