Cell-type specific mechanisms of D-serine uptake and release in the brain

Martineau, Magalie; Parpura, Vladimir; Mothet, Jean-Pierre

doi:10.3389/fnsyn.2014.00012

Cited by 91 publications

(91 citation statements)

References 102 publications

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“…Accumulating evidence suggests both neuronal and glial sources of D-serine synthesis, but recent studies point to different mechanisms of release. In astrocytes, evidence of calcium-dependent vesicular D-serine release has been reported in the hippocampus (Henneberger et al, 2010;Martineau et al, 2014) and calcium-independent D-serine release via pannexin-1 hemichannels has been reported in astrocyte cultures (Pan et al, 2015). In contrast, amino acid transporters have been implicated in neuronal D-serine release .…”

Section: Elevated Levels Of D-serine Results In Enlarged Visual Receptmentioning

confidence: 99%

“…Determining the functional source of D-serine remains a topic of extensive investigation (Ehmsen et al, 2013;Martineau et al, 2013;Balu et al, 2014;Martineau et al, 2014). Accumulating evidence suggests both neuronal and glial sources of D-serine synthesis, but recent studies point to different mechanisms of release.…”

Section: Elevated Levels Of D-serine Results In Enlarged Visual Receptmentioning

confidence: 99%

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The Gliotransmitter d-Serine Promotes Synapse Maturation and Axonal Stabilization In Vivo

et al. 2017

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The NMDAR is thought to play a key role in the refinement of connectivity in developing neural circuits. Pharmacological blockade or genetic loss-of-function manipulations that prevent NMDAR function during development result in the disorganization of topographic axonal projections. However, because NMDARs contribute to overall glutamatergic neurotransmission, such loss-of-function experiments fail to adequately distinguish between the roles played by NMDARs and neural activity in general. The gliotransmitter D-serine is a coagonist of the NMDAR that is required for NMDAR channel opening, but which cannot mediate neurotransmission on its own. Here we demonstrate that acute administration of D-serine has no immediate effect on glutamate release or AMPA-mediated neurotransmission. We show that endogenous D-serine is normally present below saturating levels in the developing visual system of the Xenopus tadpole. Using an amperometric enzymatic biosensor, we demonstrate that glutamatergic activation elevates ambient endogenous D-serine levels in the optic tectum. Chronically elevating levels of D-serine promoted synaptic maturation and resulted in the hyperstabilization of developing axon branches in the tadpole visual system. Conversely, treatment with an enzyme that degrades endogenous D-serine resulted in impaired synaptic maturation. Despite the reduction in axon arbor complexity seen in D-serine-treated animals, tectal neuron visual receptive fields were expanded, suggesting a failure to prune divergent retinal inputs. Together, these findings positively implicate NMDAR-mediated neurotransmission in developmental synapse maturation and the stabilization of axonal inputs and reveal a potential role for D-serine as an endogenous modulator of circuit refinement.

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Section: Elevated Levels Of D-serine Results In Enlarged Visual Receptmentioning

confidence: 99%

Section: Elevated Levels Of D-serine Results In Enlarged Visual Receptmentioning

confidence: 99%

The Gliotransmitter d-Serine Promotes Synapse Maturation and Axonal Stabilization In Vivo

et al. 2017

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“…For instance, the results don’t necessarily mean that gliotransmitters are released directly through Cx43 HCs. Open HCs can facilitate Ca 2+ entry (Schalper et al, 2010) that in turn could trigger Ca 2+ -dependent exocytosis of gliotransmitters indirectly (Martineau et al, 2014). Indeed, the exocytotic secretory machinery (e.g., soluble N-ethyl maleimide-sensitive fusion protein attachment protein receptor (SNARE) complex) is present in astrocytes (Hamilton, 2010) and astrocytic Ca 2+ -dependent exocytosis of glutamate, D-serine and ATP has been described in literature (Harada et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Connexin43 Hemichannels Impairs Spatial Short-Term Memory without Affecting Spatial Working Memory

Walrave

Vinken

Albertini

et al. 2016

Front. Cell. Neurosci.

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Astrocytes are active players in higher brain function as they can release gliotransmitters, which are essential for synaptic plasticity. Various mechanisms have been proposed for gliotransmission, including vesicular mechanisms as well as non-vesicular ones, for example by passive diffusion via connexin hemichannels (HCs). We here investigated whether interfering with connexin43 (Cx43) HCs influenced hippocampal spatial memory. We made use of the peptide Gap19 that blocks HCs but not gap junction channels and is specific for Cx43. To this end, we microinfused transactivator of transcription linked Gap19 (TAT-Gap19) into the brain ventricle of male NMRI mice and assessed spatial memory in a Y maze. We found that the in vivo blockade of Cx43 HCs did not affect the locomotor activity or spatial working memory in a spontaneous alternation Y maze task. Cx43 blockade did however significantly impair the spatial short-term memory in a delayed spontaneous alternation Y maze task. These results indicate that Cx43 HCs play a role in spatial short-term memory.

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“…Glutamate [and to a lesser degree aspartate (Chen et al, 2005;Patneau and Mayer, 1990)] activates excitatory glutamate receptors, with swelling-induced release of glutamate thought to play a role in pathological conditions such as stroke and spreading depression (Akita and Okada, 2014). D-serine, a co-activator of ionotropic glutamate receptors (Mothet et al, 2000), has also been suggested as potential VRAC substrate (Martineau et al, 2014;Rosenberg et al, 2010), whereas there is no clear evidence for VRAC-dependent transport of the inhibitory neurotransmitter GABA (Franco et al, 2001). Disruption of LRRC8 genes can now be used to stringently assess whether these compounds are transported by VRACs.…”

Section: Introductionmentioning

confidence: 99%

Selective transport of neurotransmitters and modulators by distinct volume-regulated LRRC8 anion channels

Lutter

Ullrich

Lueck

et al. 2017

Journal of Cell Science

132

182

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In response to swelling, mammalian cells release chloride and organic osmolytes through volume-regulated anion channels (VRACs). VRACs are heteromers of LRRC8A and other LRRC8 isoforms (LRRC8B to LRRC8E), which are co-expressed in HEK293 and most other cells. The spectrum of VRAC substrates and its dependence on particular LRRC8 isoforms remains largely unknown. We show that, besides the osmolytes taurine and myo-inositol, LRRC8 channels transport the neurotransmitters glutamate, aspartate and γ-aminobutyric acid (GABA) and the co-activator D-serine. HEK293 cells engineered to express defined subsets of LRRC8 isoforms were used to elucidate the subunit-dependence of transport. Whereas LRRC8D was crucial for the translocation of overall neutral compounds like myo-inositol, taurine and GABA, and sustained the transport of positively charged lysine, flux of negatively charged aspartate was equally well supported by LRRC8E. Disruption of LRRC8B or LRRC8C failed to decrease the transport rates of all investigated substrates, but their inclusion into LRRC8 heteromers influenced the substrate preference of VRAC. This suggested that individual VRACs can contain three or more different LRRC8 subunits, a conclusion confirmed by sequential coimmunoprecipitations. Our work suggests a composition-dependent role of VRACs in extracellular signal transduction.

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Cell-type specific mechanisms of D-serine uptake and release in the brain

Cited by 91 publications

References 102 publications

The Gliotransmitter d-Serine Promotes Synapse Maturation and Axonal Stabilization In Vivo

The Gliotransmitter d-Serine Promotes Synapse Maturation and Axonal Stabilization In Vivo

Inhibition of Connexin43 Hemichannels Impairs Spatial Short-Term Memory without Affecting Spatial Working Memory

Selective transport of neurotransmitters and modulators by distinct volume-regulated LRRC8 anion channels

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