Lipid rafts make for slippery platforms

Abstract Transposable elements colonize genomes and with time may end up being incorporated into functional regions. SINE Alu elements, which appeared in the primate lineage, are ubiquitous in the human genome and more than a thousand overlap annotated coding exons. Although almost all Alu-derived coding exons appear to be in alternative transcripts, they have been incorporated into the main coding transcript in at least 11 genes. The extent to which Alu regions are incorporated into functional proteins is unclear, but we detected reliable peptide evidence to support the translation to protein of 33 Alu-derived exons. All but one of the Alu elements for which we detected peptides were frame-preserving and there was proportionally seven times more peptide evidence for Alu elements as for other primate exons. Despite this strong evidence for translation to protein we found no evidence of selection, either from cross species alignments or human population variation data, among these Alu-derived exons. Overall, our results confirm that SINE Alu elements have contributed to the expansion of the human proteome, and this contribution appears to be stronger than might be expected over such a relatively short evolutionary timeframe. Despite this, the biological relevance of these modifications remains open to question.

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Use of Detergents to Study Membrane Rafts: The Good, the Bad, and the Ugly

Biological Chemistry ◽

10.1515/bc.2003.139 ◽

2003 ◽

Vol 384 (9) ◽

pp. 1259-1263 ◽

Cited By ~ 143

Author(s):

H. Shogomori ◽

D.A. Brown

Keyword(s):

Lipid Rafts ◽

Cell Membranes ◽

Eukaryotic Cell ◽

Membrane Rafts ◽

Ionic Detergents ◽

Wide Range ◽

Range Of Functions ◽

Acyl Chains

Abstract Eukaryotic cell membranes contain microdomains called lipid rafts, which are cholesterol-rich domains in which lipid acyl chains are tightly packed and highly extended. A variety of proteins associate preferentially with rafts, and this raft association is important in a wide range of functions. A powerful and widely used method for studying lipid rafts takes advantage of their insolubility in non-ionic detergents. Here we describe the basis of detergent insolubility, and review strengths, limitations, and unresolved puzzles regarding this method.

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What have humans done for evolutionary biology? Contributions from genes to populations

Proceedings of The Royal Society B Biological Sciences ◽

10.1098/rspb.2017.1164 ◽

2017 ◽

Vol 284 (1866) ◽

pp. 20171164 ◽

Cited By ~ 5

Author(s):

Michael Briga ◽

Robert M. Griffin ◽

Vérane Berger ◽

Jenni E. Pettay ◽

Virpi Lummaa

Keyword(s):

Natural Selection ◽

Evolutionary Biology ◽

Human Study ◽

Human Studies ◽

Human Populations ◽

Evolutionary Processes ◽

Biological Relevance ◽

Evolutionary Studies ◽

Almost All ◽

Study Designs

Many fundamental concepts in evolutionary biology were discovered using non-human study systems. Humans are poorly suited to key study designs used to advance this field, and are subject to cultural, technological, and medical influences often considered to restrict the pertinence of human studies to other species and general contexts. Whether studies using current and recent human populations provide insights that have broader biological relevance in evolutionary biology is, therefore, frequently questioned. We first surveyed researchers in evolutionary biology and related fields on their opinions regarding whether studies on contemporary humans can advance evolutionary biology. Almost all 442 participants agreed that humans still evolve, but fewer agreed that this occurs through natural selection. Most agreed that human studies made valuable contributions to evolutionary biology, although those less exposed to human studies expressed more negative views. With a series of examples, we discuss strengths and limitations of evolutionary studies on contemporary humans. These show that human studies provide fundamental insights into evolutionary processes, improve understanding of the biology of many other species, and will make valuable contributions to evolutionary biology in the future.

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Active 3ʹ–5ʹ cyclic nucleotide phosphodiesterases are present in detergent-resistant membranes of mural granulosa cells

Reproduction Fertility and Development ◽

10.1071/rd15243 ◽

2017 ◽

Vol 29 (4) ◽

pp. 778 ◽

Cited By ~ 4

Author(s):

Annick Bergeron ◽

Christine Guillemette ◽

Marc-André Sirard ◽

François J. Richard

Keyword(s):

Cell Membrane ◽

Lipid Rafts ◽

Granulosa Cell ◽

Granulosa Cells ◽

Cell Membranes ◽

Soluble Fraction ◽

Cell Signalling ◽

Membrane Microdomains ◽

Dot Blot ◽

Detergent Resistant Membranes

Lipids rafts are specialised membrane microdomains involved in cell signalling that can be isolated as detergent-resistant membranes (DRMs). The second messenger cyclic AMP (cAMP) has a central role in cell signalling in the ovary and its degradation is carried out by the phosphodiesterase (PDE) enzyme family. We hypothesised that PDEs could be functionally present in the lipid rafts of porcine mural granulosa cell membranes. PDE6C, PDE8A and PDE11A were detected by dot blot in the DRMs and the Triton-soluble fraction of the mural granulosa cells membrane and the cytosol. As shown by immunocytochemistry, PDEs showed clear immunostaining in mural granulosa cell membranes and the cytosol. Interestingly, cAMP–PDE activity was 18 times higher in the DRMs than in the Triton-soluble fraction of cell membranes and was 7.7 times higher in the cytosol than in the DRMs. cAMP–PDE activity in mural granulosa cells was mainly contributed by the PDE8 and PDE11 families. This study shows that PDEs from the PDE8 and PDE11 families are present in mural granulosa cells and that the cAMP–PDE activity is mainly contributed by the cytosol. In the cell membrane, the cAMP–PDE activity is mainly contributed by the DRMs. In addition, receptors for prostaglandin E2 and LH, two G-protein-coupled receptors, are present in lipid rafts and absent from the non-raft fraction of the granulosa cell membrane. These results suggest that in these cells, the lipid rafts exist as a cell-signalling platform and PDEs are one of the key enzyme families present in the raft.

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Correlative nanophotonic approaches to enlighten the nanoscale dynamics of living cell membranes

Biochemical Society Transactions ◽

10.1042/bst20210457 ◽

2021 ◽

Author(s):

Pamina M. Winkler ◽

María F. García-Parajo

Keyword(s):

Extracellular Matrix ◽

Cell Membrane ◽

Actin Cytoskeleton ◽

Single Molecule ◽

Living Cell ◽

Cell Membranes ◽

Cell Function ◽

Membrane Dynamics ◽

Correlation Spectroscopy ◽

Spatiotemporal Resolution

Dynamic compartmentalization is a prevailing principle regulating the spatiotemporal organization of the living cell membrane from the nano- up to the mesoscale. This non-arbitrary organization is intricately linked to cell function. On living cell membranes, dynamic domains or ‘membrane rafts' enriched with cholesterol, sphingolipids and other certain proteins exist at the nanoscale serving as signaling and sorting platforms. Moreover, it has been postulated that other local organizers of the cell membrane such as intrinsic protein interactions, the extracellular matrix and/or the actin cytoskeleton synergize with rafts to provide spatiotemporal hierarchy to the membrane. Elucidating the intricate coupling of multiple spatial and temporal scales requires the application of correlative techniques, with a particular need for simultaneous nanometer spatial precision and microsecond temporal resolution. Here, we review novel fluorescence-based techniques that readily allow to decode nanoscale membrane dynamics with unprecedented spatiotemporal resolution and single-molecule sensitivity. We particularly focus on correlative approaches from the field of nanophotonics. Notably, we introduce a versatile planar nanoantenna platform combined with fluorescence correlation spectroscopy to study spatiotemporal heterogeneities on living cell membranes at the nano- up to the mesoscale. Finally, we outline remaining future technological challenges and comment on potential directions to advance our understanding of cell membrane dynamics under the influence of the actin cytoskeleton and extracellular matrix in uttermost detail.

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Antiviral activity of Glucosylceramide synthase inhibitors against SARS-CoV-2 and other RNA virus infections

10.1101/2020.05.18.103283 ◽

2020 ◽

Cited By ~ 2

Author(s):

Einat. B. Vitner ◽

Roy Avraham ◽

Hagit Achdout ◽

Hadas Tamir ◽

Avi Agami ◽

...

Keyword(s):

Broad Spectrum ◽

Influenza A ◽

Cell Membranes ◽

Rna Viruses ◽

Rna Virus ◽

Antiviral Drugs ◽

Membrane Dynamics ◽

Biologically Active ◽

Phase Iii ◽

Glucosylceramide Synthase

AbstractThe need for antiviral drugs is real and relevant. Broad spectrum antiviral drugs have a particular advantage when dealing with rapid disease outbreaks, such as the current COVID-19 pandemic. Since viruses are completely dependent on internal cell mechanisms, they must cross cell membranes during their lifecycle, creating a dependence on processes involving membrane dynamics. Thus, in this study we examined whether the synthesis of glycosphingolipids, biologically active components of cell membranes, can serve as an antiviral therapeutic target. We examined the antiviral effect of two specific inhibitors of GlucosylCeramide synthase (GCS); (i) Genz-123346, an analogue of the FDA-approved drug Cerdelga®, (ii) GENZ-667161, an analogue of venglustat which is currently under phase III clinical trials. We found that both GCS inhibitors inhibit the replication of four different enveloped RNA viruses of different genus, organ-target and transmission route: (i) Neuroinvasive Sindbis virus (SVNI), (ii) West Nile virus (WNV), (iii) Influenza A virus, and (iv) SARS-CoV-2. Moreover, GCS inhibitors significantly increase the survival rate of SVNI-infected mice. Our data suggest that GCS inhibitors can potentially serve as a broad-spectrum antiviral therapy and should be further examined in preclinical and clinical trial. Analogues of the specific compounds tested have already been studied clinically, implying they can be fast-tracked for public use. With the current COVID-19 pandemic, this may be particularly relevant to SARS-CoV-2 infection.One Sentence SummaryAn analogue of Cerdelga®, an FDA-approved drug, is effective against a broad range of RNA-viruses including the newly emerging SARS-CoV-2.

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