Acharya Usha, Mowen Michael Beth, Nagashima Kunio, Acharya Jairaj K
Regulation of Cell Growth Laboratory, National Cancer Institute, Frederick, MD 21702, USA.
Proc Natl Acad Sci U S A. 2004 Feb 17;101(7):1922-6. doi: 10.1073/pnas.0308693100. Epub 2004 Feb 9.
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 ninaE(I17) mutants 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.
神经酰胺酶的转基因表达可抑制果蝇视 Arrestin 和磷脂酶 C 突变体中的视网膜退化。在此,我们表明,在 R1-R6 光感受器细胞中缺乏 G 蛋白受体 Rh1 的 ninaE(I17) 突变体中,神经酰胺酶的表达促进了微绒毛膜不完全形成和定位不当的成分的溶解。神经酰胺酶的表达促进了 Rh1 的内吞周转。虽然神经酰胺酶的表达有助于去除内化的视紫红质,但它并不影响在黑暗中维持的光感受器中 Rh1 的周转,在黑暗中 Rh1 未被激活,因此周转较慢且半衰期较长。因此,光感受器中神经酰胺酶表达的表型后果是由内吞作用的促进引起的。本研究为鞘脂生物合成途径介导的内吞作用调节和视网膜退化抑制提供了机制性见解。