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ANA Anatomy & Morphology --- anatomy --- cell physiology --- mechanisms --- plasma membrane --- protoplasm

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Participant à laplupartdes transmissions excitatrices, le glutamate est un essentiel au sein du système nerveux central. Cependant, il doit impérativement être éliminé de la fente synaptique, afin d'éviter des phénomènes de neurotoxicité. Cette élimination est principalement assurée par les astrocytes, qui expriment des transporteurs membranaires spécifiques. Dans les tumeurs gliales (gliomes), cette homéostasie glutamatergique est fortement perturbée. Malgré leur origine souvent astrocytaire, les cellules de gliome sont incapables de capter efficacement le glutamate et, au contraire, en libèrent des quantités importantes. Les processus biochimiques régulant les transporteurs du glutamate dans le gliome restent peu documentés. Des expériences réalisées sur des modèles recombinants proposent que la kinase activée par I'AMP (AMPK) soit capable de réguler le transport du glutamate. En outre, des études en cours au sein de notre laboratoire suggèrent que cette kinase exerce une influence sur le transport du glutamate dans des astrocytes en culture primaire. Puisque I'AMPK semble être impliquée dans la progression de divers cancers, nous avons examiné le lien éventuel entre le degré d'activation constitutive de cette enzyme dans une lignée d'astrocytome, les cellules C6, et leur faible capacité à capter le glutamate. Nous avons d'abord déterminé que I'AMPK est constitutivement plus active dans notre modèle de gliome comparativement au modèle astrocytaire. Ensuite, par le biais de la différenciation astrocytaire forcée de cette lignée de gliome, nous avons montré qu'il est possible de réprimer l'activité constitutive de l'AMPK et de diminuer également l'expression de sa sous-unité catalytique al. Cette perte d'activité de l'AMPK s'est accompagnée d'une augmentation du transport du glutamate dans ces cellules en différenciation. Finalement, la manipulation génétique de l'expression de l’AMPKα1 s'est également révélée capable d'augmenter le transport du glutamate dans le modèle de gliome, appuyant ainsi notre hypothèse. La consolidation de ces travaux reste, cependant, nécessaire afin préciser la relevance de ces observations dans le développement du gliome. Glutamate is the principal excitatory neurotransmitter in the nervous system. However, elevated extracellular concentrations of this transmitter seem to be an important cause of neuronal death in a variety of nervous system diseases. Therefore, tight regulation of glutamate concentrations is important for normal brain function and is mainly ensured by glial cells, which express high affinity glutamate transporters. ln glia-derived tumors (gliomas), glutamate homeostasis was proven to be disrupted and this correlates with a reduced expression of specific glutamate transporters. ln fact, these cells are unable to efficiently take up glutamate from the synaptic cleft, leading to excitotoxicity in the vicinity of the tumor, thus potentially favoring tumor progression. However, the mechanisms regulating glutamate transporters in glial tumors remain unknown. Previous studies performed on recombinant models suggest that the cellular energy sensor AMP-activated protein kinase (AMPK) influences the activity of glutamate transporters. Moreover, recent work in our laboratory indicates that AMPK activation promotes a decrease of cell-surface expression of glutamate transporters, in primary cultures of astrocytes. Given that AMPK has been implicated in the progression of several tumors, we here propose the hypothesis for a functional link between the constitutive activation of AMPK previously reported in glial tumors, and the impaired glutamate uptake capacity of these cancer cells. Firstly, our data showed that the AMPK activity found in a rat glioma model (C6 cell line) is constitutively higher when compared to normal rodent astrocytes. Secondly, by driving differentiation of the glioma cell line into an astrocytic phenotype, we were able to reduce this constitutive AMPK activity and the expression of its al catalytic subunit. These changes were correlated with an increased activity and expression of glutamate transporters in C6 cells undergoing differentiation. Thirdly, preliminary results showed that genetic manipulation of AMPKα1 expression in naïve C6 cells promotes their glutamate uptake capacity. Together, our data suggest a putative link between the constitutive AMPK activity observed in glioma cells and their impaired capacity to take up glutamate. Further studies, including the analysis of other glioma cell lines and human glioma samples, should help to consolidate our hypothesis.

AMP-Activated Protein Kinases --- Glutamate Plasma Membrane Transport Proteins --- Glioma

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This eBook is a collection of articles from a Frontiers Research Topic. Frontiers Research Topics are very popular trademarks of the Frontiers Journals Series: they are collections of at least ten articles, all centered on a particular subject. With their unique mix of varied contributions from Original Research to Review Articles, Frontiers Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area! Find out more on how to host your own Frontiers Research Topic or contribute to one as an author by contacting the Frontiers Editorial Office: frontiersin.org/about/contact

fatty acids --- ion channels --- ionic pumps --- PUFAs --- plasma membrane

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This eBook is a collection of articles from a Frontiers Research Topic. Frontiers Research Topics are very popular trademarks of the Frontiers Journals Series: they are collections of at least ten articles, all centered on a particular subject. With their unique mix of varied contributions from Original Research to Review Articles, Frontiers Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area! Find out more on how to host your own Frontiers Research Topic or contribute to one as an author by contacting the Frontiers Editorial Office: frontiersin.org/about/contact

Science: general issues --- Physiology --- fatty acids --- ion channels --- ionic pumps --- PUFAs --- plasma membrane

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Plasmodesmata (PD) are plant-specific intercellular nanopores defined by specialised domains of the plasma membrane (PM) and the endoplasmic reticulum (ER), both of which contain unique proteins, and probably different lipid compositions than the surrounding bulk membranes. The PD membranes form concentric tubules with a minimal outer diameter of only 50 nm, and the central ER strand constricted to ~10-15 nm, representing one of the narrowest stable membrane tubules in nature. This unique membrane architecture poses many biophysical, structural and functional questions. PM continuity across PD raises the question as to how a locally confined membrane site is established and maintained at PD. There is increasing evidence that the PM within PD may be enriched in membrane ‘rafts’ or TET web domains. Lipid rafts often function as signalling platforms, in line with the emerging view of PD as central players in plant defense responses. Lipid-lipid immiscibility could also provide a mechanism for membrane sub- compartmentalisation at PD. Intricate connections of the PM to the wall and the underlying cytoskeleton and ER may anchor the specialised domains locally. The ER within PD is even more strongly modified. Its extreme curvature suggests that it is stabilised by densely packed proteins, potentially members of the reticulon family that tubulate the cortical ER. The diameter of the constricted ER within PD is similar to membrane stalks in dynamin-mediated membrane fission during endocytosis and may need to be stabilised against spontaneous rupture. The function of this extreme membrane constriction, and the reasons why the ER is connected between plant cells remain unknown. Whilst the technically challenging search for the protein components of PD is ongoing, there has been significant recent progress in research on biological membranes that could benefit our understanding of PD function. With this Research Topic, we therefore aim to bring together researchers in the PD field and those in related areas, such as membrane biophysics, membrane composition and fluidity, protein-lipid interactions, lateral membrane heterogeneity, lipid rafts, membrane curvature, and membrane fusion/fission.

Plant cells and tissues. --- Plant cell culture. --- Plasmodesmata. --- lipid rafts --- membrane curvature --- plasmodesmata --- membrane microdomains --- plasma membrane --- protein-lipid interaction --- endoplasmic reticulum --- super-resolution microscopy