Functional identification of ASCT1 neutral amino acid transporter as the predominant system for the uptake of l-serine in rat neurons in primary culture

Yamamoto, Toshiyuki; Nishizaki, Itone; Nukada, Toshihide; Kamegaya, Etsuko; Furuya, Shigeki; Hirabayashi, Yoshio; Ikeda, Kazutaka; Hata, Hirofumi; Kobayashi, Hideaki; Sora, Ichiro; Yamamoto, Hiroyuki

doi:10.1016/j.neures.2004.02.004

Cited by 49 publications

(41 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Additionally, ASCT2 transports L-glutamine and L-asparagine with high affinity (Utsunomiya-Tate et al, 1996). ASCT1/2 are both expressed in astrocytes and neurons (Bröer et al, 1999; Weiss et al, 2001; Yamamoto et al, 2003, 2004; Gliddon et al, 2009; Shao et al, 2009). ASCT1 appears to be the predominant system for uptake of L-serine in cultured neurons (Yamamoto et al, 2004).…”

Section: Control Of Extracellular D-serine Concentrationmentioning

confidence: 99%

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

Martineau¹,

Parpura

Mothet

2014

Front. Synaptic Neurosci.

View full text Add to dashboard Cite

Accumulating evidence during the last decade established that D-serine is a key signaling molecule utilized by neurons and astroglia in the mammalian central nervous system. D-serine is increasingly appreciated as the main physiological endogenous coagonist for synaptic NMDA receptors at central excitatory synapses; it is mandatory for long-term changes in synaptic strength, memory, learning, and social interactions. Alterations in the extracellular levels of D-serine leading to disrupted cell-cell signaling are a trademark of many chronic or acute neurological (i.e., Alzheimer disease, epilepsy, stroke) and psychiatric (i.e., schizophrenia) disorders, and are associated with addictive behavior (i.e., cocaine addiction). Indeed, fine tuning of the extracellular levels of D-serine, achieved by various molecular machineries and signaling pathways, is necessary for maintenance of accurate NMDA receptor functions. Here, we review the experimental data supporting the notion that astroglia and neurons use different pathways to regulate levels of extracellular D-serine.

show abstract

Section: Control Of Extracellular D-serine Concentrationmentioning

confidence: 99%

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

Martineau¹,

Parpura

Mothet

2014

Front. Synaptic Neurosci.

View full text Add to dashboard Cite

show abstract

“…Interestingly, several transporters also function as receptors for different neurotropic retroviruses (4). The human endogenous retrovirus (HERV-W) envelope glycoprotein, Syncytin-1, binds to two receptors including the sodium-dependent transporters of polar neutral amino acids, alanine, serine, cysteine, and threonine (ASCT1 and ASCT2) (4), which are localized on both neurons and glia (5) and are known to modulate both neurotrophic (6) and neurotoxic (7) effects in the CNS.…”

Section: Ultiple Sclerosis (Ms)mentioning

confidence: 99%

The Human Endogenous Retrovirus Envelope Glycoprotein, Syncytin-1, Regulates Neuroinflammation and Its Receptor Expression in Multiple Sclerosis: A Role for Endoplasmic Reticulum Chaperones in Astrocytes

Antony

Ellestad

Hammond

et al. 2007

The Journal of Immunology

126

125

View full text Add to dashboard Cite

Retroviral envelopes are pathogenic glycoproteins which cause neuroinflammation, neurodegeneration, and endoplasmic reticulum stress responses. The human endogenous retrovirus (HERV-W) envelope protein, Syncytin-1, is highly expressed in CNS glia of individuals with multiple sclerosis (MS). In this study, we investigated the mechanisms by which Syncytin-1 mediated neuroimmune activation and oligodendrocytes damage. In brain tissue from individuals with MS, ASCT1, a receptor for Syncytin-1 and a neutral amino acid transporter, was selectively suppressed in astrocytes (p < 0.05). Syncytin-1 induced the expression of the endoplasmic reticulum stress sensor, old astrocyte specifically induced substance (OASIS), in cultured astrocytes, similar to findings in MS brains. Overexpression of OASIS in astrocytes increased inducible NO synthase expression but concurrently down-regulated ASCT1 (p < 0.01). Treatment of astrocytes with a NO donor enhanced expression of early growth response 1, with an ensuing reduction in ASCT1 expression (p < 0.05). Small-interfering RNA molecules targeting Syncytin-1 selectively down-regulated its expression, preventing the suppression of ASCT1 and the release of oligodendrocyte cytotoxins by astrocytes. A Syncytin-1-transgenic mouse expressing Syncytin-1 under the glial fibrillary acidic protein promoter demonstrated neuroinflammation, ASCT1 suppression, and diminished levels of myelin proteins in the corpus callosum, consistent with observations in CNS tissues from MS patients together with neurobehavioral abnormalities compared with wild-type littermates (p < 0.05). Thus, Syncytin-1 initiated an OASIS-mediated suppression of ASCT1 in astrocytes through the induction of inducible NO synthase with ensuing oligodendrocyte injury. These studies provide new insights into the role of HERV-mediated neuroinflammation and its contribution to an autoimmune disease.

show abstract

“…ASCT functions as a hetero-or homoexchanger [49] and there is evidence that D-serine flux is coupled to L-serine flux [21]. Also, ASCT1 and ASCT2 are localized in astrocytes where D-serine is found [50][51][52][53]. The increased extracellular D-serine levels observed here with the application of exogenous L-serine could therefore be explained by ASCT mediated heteroexchange of D-and L-serine.…”

mentioning

confidence: 91%

MeasuringD-serine efflux from mouse cortical brain slices using online microdialysis-capillary electrophoresis

O'Brien

Bowser

2006

Electrophoresis

View full text Add to dashboard Cite

Efflux of a number of important neurochemicals, including D-serine, L-serine, taurine, glutamate, and gamma-aminobutyric acid (GABA), from mouse cortical brain slices housed in a 7 microL perfusion chamber was monitored using online microdialysis-CE (MD-CE). Analyte concentrations could be measured every 20-27 s using the MD-CE instrument. Stimulation with high potassium induced increased release of D-serine. Kainic acid (KA) induced D-serine release, but this release was not blocked by 6-cyano-7-nitroquinoxaline-2,3-dione, suggesting that alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid/KA receptors do not mediate D-serine release. Application of L-serine, the precursor of D-serine, resulted in increased extracellular D-serine concentrations. L-Cysteine also increased extracellular D-serine levels in a partially Na+-dependent manner. The observed effects upon application of L-serine and L-cysteine support the involvement of ASC neutral amino acid transporters in regulating the extracellular concentration of D-serine concentration through competitive inhibition of uptake or increased release through heteroexchange.

show abstract

Functional identification of ASCT1 neutral amino acid transporter as the predominant system for the uptake of l-serine in rat neurons in primary culture

Cited by 49 publications

References 23 publications

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

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

The Human Endogenous Retrovirus Envelope Glycoprotein, Syncytin-1, Regulates Neuroinflammation and Its Receptor Expression in Multiple Sclerosis: A Role for Endoplasmic Reticulum Chaperones in Astrocytes

MeasuringD-serine efflux from mouse cortical brain slices using online microdialysis-capillary electrophoresis

Contact Info

Product

Resources

About