26 research outputs found
Zinc reverses glycine-dependent inactivation of NMDARs in cultured rat hippocampal neurons
Differential clustering of Caspr by oligodendrocytes and Schwann cells
Formation of the paranodal axoglial junction (PNJ) requires the presence of three cell adhesion molecules: the 155-kDa isoform of neurofascin (NF155) on the glial membrane and a complex of Caspr and contactin found on the axolemma. Here we report that the clustering of Caspr along myelinated axons during development differs fundamentally between the central (CNS) and peripheral (PNS) nervous systems. In cultures of Schwann cells (SC) and dorsal root ganglion (DRG) neurons, membrane accumulation of Caspr was detected only after myelination. In contrast, in oligodendrocytes (OL)/DRG neurons cocultures, Caspr was clustered upon initial glial cell contact already before myelination had begun. Premyelination clustering of Caspr was detected in cultures of oligodendrocytes and retinal ganglion cells, motor neurons, and DRG neurons as well as in mixed cell cultures of rat forebrain and spinal cords. Cocultures of oligodendrocyte precursor cells isolated from contactin- or neurofascin-deficient mice with wild-type DRG neurons showed that clustering of Caspr at initial contact sites between OL processes and the axon requires glial expression of NF155 but not of contactin. These results demonstrate that the expression of membrane proteins along the axolemma is determined by the type of the contacting glial cells and is not an intrinsic characteristic of the axon
Identification of Tmem10/opalin as an oligodendrocyte enriched gene using expression profiling combined with genetic cell ablation
Oligodendrocytes form an insulating multilamellar structure
of compact myelin around axons, which allows efficient
and rapid propagation of action potentials. However, little
is known about the molecular mechanisms operating at the
onset of myelination and during maintenance of the myelin
sheath in the adult. Here we use a genetic cell ablation
approach combined with Affymetrix GeneChip microarrays
to identify a number of oligodendrocyte-enriched genes that
may play a key role in myelination. One of the ‘‘oligogenes’’
we cloned using this approach is Tmem10/Opalin, which
encodes for a novel transmembrane glycoprotein. In situ
hybridization and RT-PCR analysis revealed that Tmem10
is selectively expressed by oligodendrocytes and that its
expression is induced during their differentiation. Developmental
immunofluorescence analysis demonstrated that
Tmem10 starts to be expressed in the white matter tracks
of the cerebellum and the corpus callosum at the onset of
myelination after the appearance of other myelin genes
such as MBP. In contrast to the spinal cord and brain,
Tmem10 was not detected in myelinating Schwann cells,
indicating that it is a CNS-specific myelin protein. In
mature oligodendrocytes, Tmem10 was present at the cell
soma and processes, as well as along myelinated internodes,
where it was occasionally concentrated at the paranodes.
In myelinating spinal cord cultures, Tmem10 was
detected in MBP-positive cellular processes that were
aligned with underlying axons before myelination commenced.
These results suggest a possible role of Tmem10
in oligodendrocyte differentiation and CNS myelination.This work was supported by grants from the
Dr. Miriam and Sheldon G. Adelson Medical Research
Foundation
Neuroscience: Astrocytes as aide-mémoires.
Memory formation is known to occur at the level of synaptic contacts between neurons. It therefore comes as a surprise that another type of brain cell, the astrocyte, is also involved in establishing memory
A metabolic gene cluster in the wheat W1 and the barley Cer-cqu loci determines beta-diketone biosynthesis and glaucousness
The glaucous appearance of wheat (Triticum aestivum) and barley (Hordeum vulgare) plants, that is the light bluish-gray look of flag leaf, stem, and spike surfaces, results from deposition of cuticular β-diketone wax on their surfaces; this phenotype is associated with high yield, especially under drought conditions. Despite extensive genetic and biochemical characterization, the molecular genetic basis underlying the biosynthesis of β-diketones remains unclear. Here, we discovered that the wheat W1 locus contains a metabolic gene cluster mediating β-diketone biosynthesis. The cluster comprises genes encoding proteins of several families including type-III polyketide synthases, hydrolases, and cytochrome P450s related to known fatty acid hydroxylases. The cluster region was identified in both genetic and physical maps of glaucous and glossy tetraploid wheat, demonstrating entirely different haplotypes in these accessions. Complementary evidence obtained through gene silencing in planta and heterologous expression in bacteria supports a model for a β-diketone biosynthesis pathway involving members of these three protein families. Mutations in homologous genes were identified in the barley eceriferum mutants defective in β-diketone biosynthesis, demonstrating a gene cluster also in the β-diketone biosynthesis Cer-cqu locus in barley. Hence, our findings open new opportunities to breed major cereal crops for surface features that impact yield and stress response
Cell Selective Conditional Null Mutations of Serine Racemase Demonstrate a Predominate Localization in Cortical Glutamatergic Neurons
Long-term potentiation depends on release of D-serine from astrocytes
International audienceLong-term potentiation (LTP) of synaptic transmission provides an experimental model for studying mechanisms of memory. The classical form of LTP relies on N-methyl-D-aspartate receptors (NMDARs), and it has been shown that astroglia can regulate their activation through Ca(2+)-dependent release of the NMDAR co-agonist D-serine. Release of D-serine from glia enables LTP in cultures and explains a correlation between glial coverage of synapses and LTP in the supraoptic nucleus. However, increases in Ca(2+) concentration in astroglia can also release other signalling molecules, most prominently glutamate, ATP and tumour necrosis factor-alpha, whereas neurons themselves can synthesize and supply D-serine. Furthermore, loading an astrocyte with exogenous Ca(2+) buffers does not suppress LTP in hippocampal area CA1 (refs 14-16), and the physiological relevance of experiments in cultures or strong exogenous stimuli applied to astrocytes has been questioned. The involvement of glia in LTP induction therefore remains controversial. Here we show that clamping internal Ca(2+) in individual CA1 astrocytes blocks LTP induction at nearby excitatory synapses by decreasing the occupancy of the NMDAR co-agonist sites. This LTP blockade can be reversed by exogenous D-serine or glycine, whereas depletion of D-serine or disruption of exocytosis in an individual astrocyte blocks local LTP. We therefore demonstrate that Ca(2+)-dependent release of D-serine from an astrocyte controls NMDAR-dependent plasticity in many thousands of excitatory synapses nearby