SREBPs are membrane bound transcription factors that are crucial for normal lipid synthesis in animal cells. Here, we show that Drosophila lacking dSREBP die before the third larval instar. Mutant larvae exhibit pronounced growth defects prior to lethality, along with substantial deficits in the transcription of genes required for fatty acid synthesis. Compared to wild-type larvae, mutants contain markedly less fatty acid, although its composition is unaltered. Dietary supplementation with fatty acids rescues mutants to adulthood. The most effective fatty acid, oleate, rescues 80% of homozygotes. Rescue by dSREBP requires expression only in fat body and gut. Larvae expressing dSREBP prior to pupariation complete development and are viable as adults even when dSREBP expression is subsequently extinguished. The role, if any, of dSREBP in adults is not yet apparent. These data indicate that dSREBP deficiency renders Drosophila larvae auxotrophic for fatty acids.
During infection by diverse viral families, RNA replication occurs on the surface of virally induced cytoplasmic membranes of cellular origin. How this process is regulated, and which cellular factors are required, has been unclear. Moreover, the host–pathogen interactions that facilitate the formation of this new compartment might represent critical determinants of viral pathogenesis, and their elucidation may lead to novel insights into the coordination of vesicular trafficking events during infection. Here we show that in Drosophila cells, Drosophila C virus remodels the Golgi apparatus and forms a novel vesicular compartment, on the surface of which viral RNA replication takes place. Using genome-wide RNA interference screening, we found that this step in the viral lifecycle requires at least two host encoded pathways: the coat protein complex I (COPI) coatamer and fatty acid biosynthesis. Our results integrate, clarify, and extend numerous observations concerning the cell biology of viral replication, allowing us to conclude that the coupling of new cellular membrane formation with the budding of these vesicles from the Golgi apparatus allows for the regulated generation of this new virogenic organelle, which is essential for viral replication. Additionally, because these pathways are also limiting in flies and in human cells infected with the related RNA virus poliovirus, they may represent novel targets for antiviral therapies.
Invariant natural killer T (iNKT) cells recognize self lipid antigens presented by CD1d molecules. The nature of the self-antigens involved in the development and maturation of iNKT cells is poorly defined. Lysophospholipids are self-antigens presented by CD1d that are generated through the action of phospholipases A1 and A2. Lysosomal phospholipase A2 (LPLA2, group XV phospholipase A2) resides in the endocytic system, the main site where CD1d antigen acquisition occurs, suggesting that it could be particularly important in CD1d function. We find that Lpla2 −/− mice show a decrease in iNKT cell numbers that is neither the result of a general effect on the development of lymphocyte populations nor of effects on CD1d expression. However, endogenous lipid antigen presentation by CD1d is reduced in the absence of LPLA2. Our data suggest that LPLA2 plays a role in the generation of CD1d complexes with thymic lipids required for the normal selection and maturation of iNKT cells.antigen processing | lipid storage disease C D1d molecules are β 2 -microglobulin (β 2 m)-associated MHC class I homologs that bind lipid antigens and recycle between the plasma membrane and endocytic compartments. Endogenous and exogenous lipid binding can occur during transit through the secretory pathway and in the endocytic system, which is the main site of antigen loading (1). CD1d-lipid complexes are recognized by natural killer T (NKT) cells, a subset of T cells that shares characteristics of both the innate and adaptive arms of the immune system. NKT cells rapidly respond to stimulation by antigenpresenting cells (APCs) and release cytokines that can alter the strength and character of immune responses. They do so by transactivating, for example, NK cells, CD4+ and CD8 + T cells, and B cells, and by shifting cytokine responses to or from T helper (Th)1, Th2, and Th17 profiles. NKT cells have been shown to participate in inflammation, autoimmunity, cancer, and infectious diseases (2-4), and are characterized by the expression of both T-cell receptor (TCR) and NK cell markers. There are two main types: type I or invariant (iNKT), which express a semi-invariant TCR (Vα14-Jα18 in mice and Vα24-Jα18 in humans, paired with a restricted set of TCR-β chains, Vβ8.2, -7, or -2 in mice and Vβ11 in humans), and type II or noninvariant NKT cells that express more diverse TCRs (5-13).iNKT cells arise from double-positive (DP; CD4
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.