Sterol transfer by atypical cholesterol-binding NPC2 proteins in coral-algal symbiosis.
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ABSTRACT:
SUBMITTER: Hambleton EA
PROVIDER: S-EPMC6548501 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Niemann--Pick C disease is an inherited disorder in which cholesterol and other lipids accumulate in the late endosomal/lysosomal compartment. Recently, cyclodextrins (CD) have been shown to reduce symptoms and extend lifespan in animal models of the disease. In the present studies we examined the mechanism of sterol transport by CD using in vitro model systems and fluorescence spectroscopy and NPC2-deficient fibroblasts. We demonstrate that cholesterol transport from the lysosomal cholesterol-binding protein NPC2 to CD occurs via aqueous diffusional transfer and is very slow; the rate-limiting step appears to be dissociation of cholesterol from NPC2, suggesting that specific interactions between NPC2 and CD do not occur. In contrast, the transfer rate of the fluorescent cholesterol analogue dehydroergosterol (DHE) from CD to phospholipid membranes is very rapid and is directly proportional to the acceptor membrane concentration, as is DHE transfer from membranes to CD. Moreover, CD dramatically increases the rate of sterol transfer between membranes, with rates that can approach those mediated by NPC2. The results suggest that sterol transfer from CD to membranes occurs by a collisional transfer mechanism involving direct interaction of CD with membranes, similar to that shown previously for NPC2. For CD, however, absolute rates are slower compared to NPC2 for a given concentration, and the lysosomal phospholipid lysobisphosphatidic acid (LBPA) does not stimulate rates of sterol transfer between membranes and CD. As expected from the apparent absence of interaction between CD and NPC2, the addition of CD to NPC2-deficient fibroblasts rapidly rescued the cholesterol accumulation phenotype. Thus, the recent observations of CD efficacy in mouse models of NPC disease are likely the result of CD enhancement of cholesterol transport between membranes, with rapid sterol transfer occurring during CD--membrane interactions.
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Project description:Background: The molecular machinery underpinning the establishment of this relationship is not well understood. This is especially true of the symbiont side, as previous attempts to understand the interaction between coral larvae and Symbiodiniaceae have focused nearly exclusively on the host Results: In the current study, we utilised dual RNA-seq approach to study both symbiont and coral transcriptomes during symbiosis establishment. The transcriptomic response of C. goreaui to the symbiotic state was complex, the most obvious feature of which was extensive and generalized downregulation of gene expression. Included in this “symbiosis-derived transcriptional repression” were a range of stress response and immune-related genes. In contrast, a range of genes implicated in metabolism were upregulated in the symbiotic state. Consistent with previous ecological studies, this transcriptomic response of C. goreaui suggests that active translocation of metabolites to the host may begin early in the colonization process, and thus that the mutualistic relationship is established at the larval stage. The coral data imply the involvement of some SCRiP family members in the colonisation process and support the hypothesis that immune-suppression and arrest of phagosome maturation play important roles during the establishment of compatible symbioses. Conclusions: This study provides novel insights into the transcriptomic remodelling that occurs in C. goreaui during transition to a symbiotic lifestyle, with important implications for understanding the establishment of symbiosis between corals and their dinoflagellate partners.
2020-08-13 | GSE145030 | GEO
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Project description:To clarify the establishment process of coral-algal symbiotic relationships, coral transcriptome changes during increasing algal symbiont densities were examined in juvenile corals following inoculation with the algae Symbiodinium goreaui (clade C) and S. trenchii (clade D), and comparison of their transcriptomes with aposymbiotic corals by RNA-sequencing. Since Symbiodinium clades C and D showed very different rates of density increase, comparisons were made of early onsets of both symbionts, revealing that the host behaved differently for each. RNA-sequencing showed that the number of differentially-expressed genes in corals colonized by clade D increased ca. two-fold from 10 to 20 days, whereas corals with clade C showed unremarkable changes consistent with a slow rate of density increase. The data revealed dynamic metabolic changes in symbiotic corals. In addition, the endocytosis pathway was also upregulated, while lysosomal digestive enzymes and the immune system tended to be downregulated as the density of clade D algae increased. The present dataset provides an enormous number of candidate symbiosis-related molecules that exhibit the detailed process by which coral-algal endosymbiosis is established.
| S-EPMC6235891 | biostudies-literature
Project description:Background: The molecular machinery underpinning the establishment of this relationship is not well understood. This is especially true of the symbiont side, as previous attempts to understand the interaction between coral larvae and Symbiodiniaceae have focused nearly exclusively on the host Results: The transcriptomic response of C. goreaui to the symbiotic state was complex, the most obvious feature of which was extensive and generalized downregulation of gene expression. Included in this “symbiosis-derived transcriptional repression” were a range of stress response and immune-related genes. In contrast, a range of genes implicated in metabolism were upregulated in the symbiotic state. Consistent with previous ecological studies, this transcriptomic response of C. goreaui suggests that active translocation of metabolites to the host may begin early in the colonization process, and thus that the mutualistic relationship is established at the larval stage Conclusions: This study provides novel insights into the transcriptomic remodelling that occurs in C. goreaui during transition to a symbiotic lifestyle, with important implications for understanding the establishment of symbiosis between corals and their dinoflagellate partners.
2020-05-31 | GSE143202 | GEO