A neuronal thermostat controls membrane fluidity in C. elegans

SummaryAn organisms’ ability to adapt to heat can be key to its survival. Cells adapt to temperature shifts by adjusting lipid desaturation levels and the fluidity of membranes in a process that is thought to be controlled cell autonomously. We have discovered that subtle, step-wise increments in ambient temperature can lead to the conserved heat shock response being activated in head neurons of C. elegans. This response is exactly opposite to the expression of the lipid desaturase FAT-7 in the worm’s gut. We find that the over-expression of the master regulator of this response, Hsf-1, in head neurons, causes extensive fat remodeling to occur across tissues. These changes include a decrease in FAT-7 expression and a shift in the levels of unsaturated fatty acids in the plasma membrane. These shifts are in line with membrane fluidity requirements to survive in warmer temperatures. We have identified that the cGMP receptor, TAX-2/TAX-4, as well as TGF-β/BMP signaling, as key players in the transmission of neuronal stress to peripheral tissues. This is the first study to suggest that a thermostat-based mechanism can centrally coordinate membrane fluidity in response to warm temperatures across tissues in multicellular animals.

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Palmitic acid causes increased dihydroceramide levels when desaturase expression is directly silenced or indirectly lowered by silencing AdipoR2

Lipids in Health and Disease ◽

10.1186/s12944-021-01600-y ◽

2021 ◽

Vol 20 (1) ◽

Author(s):

Mario Ruiz ◽

Marcus Henricsson ◽

Jan Borén ◽

Marc Pilon

Keyword(s):

Palmitic Acid ◽

Unsaturated Fatty Acids ◽

Cultured Cells ◽

De Novo ◽

Strong Increase ◽

Over Expression ◽

C Elegans ◽

Ceramide Synthesis ◽

Positive Regulators ◽

Rate Limiting

Abstract Background AdipoR1 and AdipoR2 (AdipoRs) are plasma membrane proteins often considered to act as adiponectin receptors with a ceramidase activity. Additionally, the AdipoRs and their yeast and C. elegans orthologs are emerging as membrane homeostasis regulators that counter membrane rigidification by promoting fatty acid desaturation and incorporation of unsaturated fatty acids into phospholipids, thus restoring fluidity. Methods Using cultured cells, the effects of AdipoR silencing or over-expression on the levels and composition of several sphingolipid classes were examined. Results AdipoR2 silencing in the presence of exogenous palmitic acid potently causes increased levels of dihydroceramides, a ceramide precursor in the de novo ceramide synthesis pathway. Conversely, AdipoR2 over-expression caused a depletion of dihydroceramides. Conclusions The results are consistent with AdipoR2 silencing leading to increased intracellular supply of palmitic acid that in turn leads to increased dihydroceramide synthesis via the rate-limiting serine palmitoyl transferase step. In agreement with this model, inhibiting the desaturase SCD or SREBF1/2 (positive regulators of SCD) also causes a strong increase in dihydroceramide levels.

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Faculty Opinions recommendation of Neuronal serotonin release triggers the heat shock response in C. elegans in the absence of temperature increase.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.725297422.793503580 ◽

2015 ◽

Author(s):

Robert K Herman

Keyword(s):

Heat Shock ◽

Heat Shock Response ◽

Temperature Increase ◽

Serotonin Release ◽

C Elegans ◽

Shock Response

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The neogenin/DCC homolog UNC-40 promotes BMP signaling via the RGM protein DRAG-1 in C. elegans

Development ◽

10.1242/dev.099838 ◽

2013 ◽

Vol 140 (19) ◽

pp. 4070-4080 ◽

Cited By ~ 17

Author(s):

Chenxi Tian ◽

Herong Shi ◽

Shan Xiong ◽

Fenghua Hu ◽

Wen-Cheng Xiong ◽

...

Keyword(s):

Bmp Signaling ◽

C Elegans

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Mutagenesis and Imaging Studies of BMP Signaling Mechanisms in C. elegans

Methods in Molecular Biology - Bone Morphogenetic Proteins ◽

10.1007/978-1-4939-8904-1_6 ◽

2018 ◽

pp. 51-73 ◽

Cited By ~ 1

Author(s):

Cathy Savage-Dunn ◽

Ryan J. Gleason ◽

Jun Liu ◽

Richard W. Padgett

Keyword(s):

Bmp Signaling ◽

Imaging Studies ◽

C Elegans ◽

Signaling Mechanisms

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Dietary fatty acids promote lipid droplet diversity through seipin enrichment in an ER subdomain

10.1101/424663 ◽

2018 ◽

Author(s):

Zhe Cao ◽

Yan Hao ◽

Yiu Yiu Lee ◽

Pengfei Wang ◽

Xuesong Li ◽

...

Keyword(s):

Fatty Acids ◽

Polyunsaturated Fatty Acids ◽

Lipid Droplet ◽

Mammalian Cells ◽

Dietary Fatty Acids ◽

Fat Storage ◽

Over Expression ◽

C Elegans ◽

Cyclopropane Fatty Acids ◽

Host Metabolism

AbstractExogenous metabolites from microbial and dietary origins have profound effects on host metabolism. Here, we report that a sub-population of lipid droplets (LDs), which are conserved organelles for fat storage, is defined by metabolites-driven targeting of theC. elegansseipin ortholog, SEIP-1. Loss of SEIP-1 function reduced the size of a subset of LDs while over-expression of SEIP-1 had the opposite effect. Ultrastructural analysis revealed SEIP-1 enrichment in an endoplasmic reticulum (ER) subdomain, which co-purified with LDs. Analyses ofC. elegansand bacterial genetic mutants indicated a requirement of polyunsaturated fatty acids (PUFAs) and microbial cyclopropane fatty acids (CFAs) for SEIP-1 enrichment, as confirmed by dietary supplementation experiments. In mammalian cells, heterologous expression of SEIP-1 promoted lipid droplet expansion from ER subdomains in a conserved manner. Our results suggest that microbial and polyunsaturated fatty acids serve unexpected roles in regulating cellular fat storage by enforcing LD diversity.

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HSPA9/Mortalin Mediates Axo-Protection by Modulating Mitochondrial Dynamics in Neurons

10.21203/rs.3.rs-119629/v1 ◽

2020 ◽

Author(s):

Cécile Ferré ◽

Anne Thouard ◽

Alexandre Bétourné ◽

Pascale Belenguer ◽

Marie-Christine Miquel ◽

...

Keyword(s):

Mitochondrial Dynamics ◽

Direct Action ◽

Mitochondrial Morphology ◽

Neuronal Cultures ◽

Mitochondrial Fragmentation ◽

Primary Neuronal Cultures ◽

Over Expression ◽

Neuronal Fate ◽

Axonal Compartment ◽

Neuronal Stress

Abstract Mortalin is a mitochondrial chaperone protein involved in quality control of proteins imported into the mitochondrial matrix, which was recently described as a sensor of neuronal stress. Mortalin is down-regulated in neurons of patients with neurodegenerative diseases and levels of Mortalin expression are correlated with neuronal fate in animal models of Alzheimer's disease or cerebral ischemia. To date, however, the links between Mortalin levels, its impact on mitochondrial function and morphology and, ultimately, the initiation of neurodegeneration, are still unclear. In the present study, we used lentiviral vectors to over- or under-express Mortalin in primary neuronal cultures. We first analyzed the early events of neurodegeneration in the axonal compartment, using oriented neuronal cultures grown in microfluidic-based devices. We observed that Mortalin down-regulation induced mitochondrial fragmentation and axonal damage, whereas its over-expression conferred protection against axonal degeneration mediated by oxidative stress. We next demonstrated that Mortalin levels modulated mitochondrial morphology by a direct action on DRP1 phosphorylation, thereby further illustrating the crucial implication of mitochondrial dynamics on neuronal fate in degenerative diseases.

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Enterotoxin B production by Staphylococcus aureus under controlled fatty acid nutrition induced by cerulenin

Canadian Journal of Microbiology ◽

10.1139/m77-171 ◽

1977 ◽

Vol 23 (9) ◽

pp. 1145-1150 ◽

Cited By ~ 2

Author(s):

Robert A. Altenbern

Keyword(s):

Fatty Acids ◽

Staphylococcus Aureus ◽

Fatty Acid ◽

Membrane Fluidity ◽

Unsaturated Fatty Acid ◽

Unsaturated Fatty Acids ◽

Basal Medium ◽

Aureus Strain ◽

Enterotoxin B ◽

Fatty Acid Supplement

Cells of Staphylococcus aureus, strain S-6, can grow in the presence of 100 μg of cerulenin/ml if the basal medium is supplemented with certain saturated or unsaturated fatty acids. The production of enterotoxin B (SEB) is markedly influenced by both the ratio of saturated to unsaturated fatty acid and by the melting point of the unsaturated fatty acid supplement. The results presented suggest that a certain degree of membrane fluidity promotes maximum SEB production and that greater or lesser degrees of membrane fluidity prohibit substantial SEB formation but fail to affect final growth density.

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INCREASE IN HSP25 EXTENDS LIFESPAN AND IMPROVES RESPONSE TO TAU TOXICITY THROUGH A CELL, NON-AUTONOMOUS MECHANISM

Innovation in Aging ◽

10.1093/geroni/igz038.2678 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

pp. S730-S730

Author(s):

Karl Rodriguez

Keyword(s):

Stress Response ◽

Protein Aggregation ◽

Cell Types ◽

Over Expression ◽

C Elegans ◽

Expression Of Genes ◽

Stress Response Pathway ◽

A Cell ◽

Cytotoxic Proteins ◽

Improve Health

Abstract The accrual of aggregation-prone cytotoxic proteins underlies neural pathologies seen in aging, Alzheimer’s disease and other dementias. Recent evidence indicates that heat shock protein 25kDa (HSP25) interacts with tau. To demonstrate a causal role for HSP25 in these pathologies, we overexpressed HSP25 protein in worms. This manipulation led to an increase in life span. Moreover, the longevity-effect was associated with increased expression of genes downstream of the SKN-1/Nrf2 stress-response transcription factor. HSP25 over-expression also reduces aggregate pathology and extends lifespan in a C. elegans neuronal-specific, aggregate-prone tau model . We propose that over-expression of HSP25 could provide protection from protein aggregation induced neurodegeneration. However, it is not yet clear whether this HSP25 effect could be efficaciously provided exogenously by other cell types. Thus, we will test whether increased peripheral HSP25 will reduce protein aggregation and stimulate a global Skn-1 stress-response pathway, reduce toxicity in neurons, and improve health outcomes.

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Tissue- and paralogue-specific functions of acyl-CoA-binding proteins in lipid metabolism in Caenorhabditis elegans

Biochemical Journal ◽

10.1042/bj20102099 ◽

2011 ◽

Vol 437 (2) ◽

pp. 231-241 ◽

Cited By ~ 26

Author(s):

Ida C. Elle ◽

Karina T. Simonsen ◽

Louise C. B. Olsen ◽

Pernille K. Birck ◽

Sidse Ehmsen ◽

...

Keyword(s):

Caenorhabditis Elegans ◽

Unsaturated Fatty Acids ◽

Expression Patterns ◽

High Specificity ◽

Tissue Expression ◽

Yeast Cells ◽

Loss Of Function ◽

C Elegans ◽

Eukaryotic Species ◽

Quadruple Mutant

ACBP (acyl-CoA-binding protein) is a small primarily cytosolic protein that binds acyl-CoA esters with high specificity and affinity. ACBP has been identified in all eukaryotic species, indicating that it performs a basal cellular function. However, differential tissue expression and the existence of several ACBP paralogues in many eukaryotic species indicate that these proteins serve distinct functions. The nematode Caenorhabditis elegans expresses seven ACBPs: four basal forms and three ACBP domain proteins. We find that each of these paralogues is capable of complementing the growth of ACBP-deficient yeast cells, and that they exhibit distinct temporal and tissue expression patterns in C. elegans. We have obtained loss-of-function mutants for six of these forms. All single mutants display relatively subtle phenotypes; however, we find that functional loss of ACBP-1 leads to reduced triacylglycerol (triglyceride) levels and aberrant lipid droplet morphology and number in the intestine. We also show that worms lacking ACBP-2 show a severe decrease in the β-oxidation of unsaturated fatty acids. A quadruple mutant, lacking all basal ACBPs, is slightly developmentally delayed, displays abnormal intestinal lipid storage, and increased β-oxidation. Collectively, the present results suggest that each of the ACBP paralogues serves a distinct function in C. elegans.

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