Phospholipid Homeostasis Regulates Dendrite Morphogenesis in Drosophila Sensory Neurons

Meltzer, Shan; Bagley, Joshua A.; Pérez, Gerardo López; DeVault, Laura; Guo, Yanmeng; Jan, Yuh Nung; Jan, Yuh-Nung

doi:10.1016/j.celrep.2017.09.089

Cited by 34 publications

(36 citation statements)

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“…Taken together, our studies provide in vivo evidence for the activity-dependent transcriptional regulation of neuronal lipo-protein receptors, a mechanism for augmenting the capacity of lipoprotein uptake in response to alterations of synaptic activity. Given the importance of lipid homeostasis in the development and maintenance of neuronal structure and function, as well as the evolutionarily conserved molecular machinery involved in its regulation ( Bailey et al, 2015 ; Meltzer et al, 2017 ; Welte, 2015 ), our findings provide a set of molecular targets for studies related to neuronal adaptive responses and have important implications in both neural development and neurodegeneration.…”

Section: Introductionmentioning

confidence: 93%

Transcriptional Regulation of Lipophorin Receptors Supports Neuronal Adaptation to Chronic Elevations of Activity

et al. 2018

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SUMMARY Activity-dependent modifications strongly influence neural development. However, molecular programs underlying their context and circuit-specific effects are not well understood. To study global transcriptional changes associated with chronic elevation of synaptic activity, we performed cell-type-specific transcriptome profiling of Drosophila ventral lateral neurons (LNvs) in the developing visual circuit and identified activity-modified transcripts that are enriched in neuron morphogenesis, circadian regulation, and lipid metabolism and trafficking. Using bioinformatics and genetic analyses, we validated activity-induced isoform-specific upregulation of Drosophila lipophorin receptors LpR1 and LpR2, the homologs of mammalian low-density lipoprotein receptor (LDLR) family proteins. Furthermore, our morphological and physiological studies uncovered critical functions of neuronal lipophorin receptors (LpRs) in maintaining the structural and functional integrities in neurons challenged by chronic elevations of activity. Together, our findings identify LpRs as molecular targets for activity-dependent transcriptional regulation and reveal the functional significance of cell-type-specific regulation of neuronal lipid uptake in experience-dependent plasticity and adaptive responses.

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Section: Introductionmentioning

confidence: 93%

Transcriptional Regulation of Lipophorin Receptors Supports Neuronal Adaptation to Chronic Elevations of Activity

et al. 2018

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“…Accordingly, metabolic pathways of TAG are not independent from the effects of the presence of structural lipids such as glycerophospholipids or sphingolipids, which may interact with TAG metabolism at multiple levels. A prominent example of this interconnection is the repression of SREBP activity by the major Drosophila membrane lipid PE, which leads to tissue-autonomous or global alterations in de novo lipogenesis and TAG storage (Lim et al 2011;Meltzer et al 2017;Ziegler et al 2017). Likewise, PC, the second most abundant glycerophospholipid in Drosophila membranes, has been identified as a critical modulator of TAG storage.…”

Section: Future Perspectivesmentioning

confidence: 99%

Triacylglycerol Metabolism in Drosophila melanogaster

2018

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Triacylglycerol (TAG) is the most important caloric source with respect to energy homeostasis in animals. In addition to its evolutionarily conserved importance as an energy source, TAG turnover is crucial to the metabolism of structural and signaling lipids. These neutral lipids are also key players in development and disease. Here, we review the metabolism of TAG in the Drosophila model system. Recently, the fruit fly has attracted renewed attention in research due to the unique experimental approaches it affords in studying the tissue-autonomous and interorgan regulation of lipid metabolism in vivo. Following an overview of the systemic control of fly body fat stores, we will cover lipid anabolic, enzymatic, and regulatory processes, which begin with the dietary lipid breakdown and de novo lipogenesis that results in lipid droplet storage. Next, we focus on lipolytic processes, which mobilize storage TAG to make it metabolically accessible as either an energy source or as a building block for biosynthesis of other lipid classes. Since the buildup and breakdown of fat involves various organs, we highlight avenues of lipid transport, which are at the heart of functional integration of organismic lipid metabolism. Finally, we draw attention to some "missing links" in basic neutral lipid metabolism and conclude with a perspective on how fly research can be exploited to study functional metabolic roles of diverse lipids.

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“…In the three brain regions, we found that glycerophospholipid metabolism was down-regulated in schizophrenia microbiota recipient mice compared with healthy microbiota recipient mice. Emerging studies have demonstrated that glycerophospholipids are involved in the initiation and elongation of dendritic spines 31,32. Our findings suggest that dysbiosis of the gut microbiota may participate in the pathogenesis of schizophrenia by modulating the growth of dendritic spines.…”

Section: Discussionmentioning

confidence: 51%

<p>Alterations Of Glycerophospholipid And Fatty Acyl Metabolism In Multiple Brain Regions Of Schizophrenia Microbiota Recipient Mice</p>

Liang

Huang

Tan

et al. 2019

NDT

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BackgroundSchizophrenia is a debilitating psychiatric disorder characterized by molecular and anatomical abnormalities of multiple brain regions. Our recent study showed that dysbiosis of the gut microbiota contributes to the onset of schizophrenia-relevant behaviors, but the underlying mechanisms remain largely unknown.PurposeThis study aimed to investigate how gut microbiota shapes metabolic signatures in multiple brain regions of schizophrenia microbiota recipient mice.MethodsGas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS) were used to compare the metabolic signatures in the cortex, cerebellum and striatum of schizophrenia microbiota and healthy microbiota recipient mice. Enrichment analysis was further conducted to uncover the crucial metabolic pathways related to schizophrenia-relevant behaviors.ResultsWe found that the metabolic phenotypes of these three regions were substantially different in schizophrenia microbiota recipient mice from those in healthy microbiota recipient mice. In total, we identified 499 differential metabolites that could discriminate the two groups in the three brain regions. These differential metabolites were mainly involved in glycerophospholipid and fatty acyl metabolism. Moreover, we found four of fatty acyl metabolites that were consistently altered in the three brain regions.ConclusionTaken together, our study suggests that alterations of glycerophospholipid and fatty acyl metabolism are implicated in the onset of schizophrenia-relevant behaviors, which may provide a new understanding of the etiology of schizophrenia.

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Phospholipid Homeostasis Regulates Dendrite Morphogenesis in Drosophila Sensory Neurons

Cited by 34 publications

References 36 publications

Transcriptional Regulation of Lipophorin Receptors Supports Neuronal Adaptation to Chronic Elevations of Activity

Transcriptional Regulation of Lipophorin Receptors Supports Neuronal Adaptation to Chronic Elevations of Activity

Triacylglycerol Metabolism in Drosophila melanogaster

<p>Alterations Of Glycerophospholipid And Fatty Acyl Metabolism In Multiple Brain Regions Of Schizophrenia Microbiota Recipient Mice</p>

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