Molecular Analysis of System N Suggests Novel Physiological Roles in Nitrogen Metabolism and Synaptic Transmission

Chaudhry, Farrukh A.; Reimer, Richard J.; Križaj, David; Barber, Diane L.; Storm‐Mathisen, Jon; Copenhagen, David R.; Edwards, Robert H.

doi:10.1016/s0092-8674(00)81674-8

Cited by 302 publications

(375 citation statements)

References 45 publications

Supporting

Mentioning

351

Contrasting

Unclassified

Order By: Relevance

“…A fragment of the EST sequence AA190522 was amplified by PCR from fetal human brain cDNA and used to screen a rat brain cDNA library (Chaudhry et al, 1999). Sequence analysis indicated that one cDNA contained the entire open reading frame with an additional 140 bp 5Ј untranslated region (UTR) and an 820 bp 3Ј UTR.…”

Section: Methodsmentioning

confidence: 99%

“…Measurement of pHi. Na ϩ /H ϩ exchanger-deficient PS120 cells were grown in DM EM with 5% fetal bovine serum, transfected with N-terminally hemagglutinin (HA)-tagged SA1, SA2, or SN1 cloned in the eukaryotic expression vector pcDNA3, and stable transformants selected in the neomycin analog G418 (Chaudhry et al, 1999). Colonies were picked after selection for 2-3 weeks and screened with commercially available antibodies to the HA epitope (Babco, Richmond, CA).…”

Section: Methodsmentioning

confidence: 99%

“…Recent work has implicated the protein responsible for classical amino acid transport System N (SN1) in glutamine efflux from astrocytes (Chaudhry et al, 1999). Although System N was originally characterized as a Na ϩ -dependent uptake activity sensitive to inhibition by low pH, the analysis of intracellular pH (pH i ) showed that SN1 also acts as a H ϩ exchanger (Chaudhry et al, 1999).…”

mentioning

confidence: 99%

“…Although System N was originally characterized as a Na ϩ -dependent uptake activity sensitive to inhibition by low pH, the analysis of intracellular pH (pH i ) showed that SN1 also acts as a H ϩ exchanger (Chaudhry et al, 1999). In addition, SN1 appears to mediate flux reversal induced simply by the removal of external glutamine, and the electroneutrality conferred by H ϩ exchange may contribute to the ease of flux reversal (Chaudhry et al, 1999). Together with its expression on astrocytes, these observations suggest that SN1 confers the efflux of glutamine from glia required to sustain the glutamineglutamate cycle.…”

mentioning

confidence: 99%

See 3 more Smart Citations

Glutamine Uptake by Neurons: Interaction of Protons with System A Transporters

et al. 2002

View full text Add to dashboard Cite

Astrocytes provide the glutamine required by neurons to synthesize glutamate and GABA. However, the mechanisms involved in glutamine transfer from glia to neurons have remained poorly understood. Recent work has implicated the System N transporter SN1 in the efflux of glutamine from astrocytes and the very closely related System A transporters SA1 and SA2 in glutamine uptake by neurons. To understand how these closely related proteins mediate flux in different directions, we have examined their ionic coupling. In contrast to the electroneutral exchange of H ϩ for Na ϩ and neutral amino acid catalyzed by SN1, we now show that SA1 and SA2 do not couple H ϩ movement to amino acid flux. As a result, SA1 and SA2 are electrogenic and do not mediate flux reversal as readily as SN1. Differences between System N and A transporters in coupling to H ϩ thus contribute to the delivery of glutamine from glia to neurons. Nonetheless, although they are not transported, H ϩ inhibit SA1 and SA2 by competing with Na ϩ .

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Glutamine Uptake by Neurons: Interaction of Protons with System A Transporters

et al. 2002

View full text Add to dashboard Cite

show abstract

“…Briefly, the glutamate released into the synaptic space by presynaptic neurons induces post-synaptic signaling through glutamate receptors, and is cleared by astrocytic excitatory amino acid transporters (EAAT1 and EAAT2, (Gegelashvili et al, 2007 andRothstein et al, 1994)), and then converted into glutamine through GS. The non-neuroactive glutamine is released into the extracellular space through astrocyte glutamine transporters (N and ASC-system transporter SN-1, SN-2 and ASCT2 (Chaudhry et al, 1999, Cubelos et al, 2005and Dolińska et al, 2004), and taken up by neurons (sodium-coupled amino acid transporter, SAT/ATA (Varoqui et al, 2000)), where it is converted back to glutamate via the action of PAG, in order to replenish the neurotransmitter pool. Therefore, astrocytic glutamate uptake prevents glutamate accumulation in the synaptic cleft and over-excitation of the postsynaptic neuronal receptors (Fig.…”

Section: Glutamine/glutamatementioning

confidence: 99%

Brain edema in acute liver failure and chronic liver disease: Similarities and differences

Bosoi

Rose

2013

Neurochemistry International

View full text Add to dashboard Cite

Hepatic encephalopathy (HE) is a complex neuropsychiatric syndrome that typically develops as a result of acute liver failure or chronic liver disease. Brain edema is a common feature associated with HE. In acute liver failure, brain edema contributes to an increase in intracranial pressure, which can fatally lead to brain stem herniation. In chronic liver disease, intracranial hypertension is rarely observed, even though brain edema may be present. This discrepancy in the development of intracranial hypertension in acute liver failure versus chronic liver disease suggests that brain edema plays a different role in relation to the onset of HE. Furthermore, the pathophysiological mechanisms involved in the development of brain edema in acute liver failure and chronic liver disease are dissimilar. This review explores the types of brain edema, the cells, and pathogenic factors involved in its development, while emphasizing the differences in acute liver failure versus chronic liver disease. The implications of brain edema developing as a neuropathological consequence of HE, or as a cause of HE, are also discussed. HighlightsBrain edema is a common feature in ALF and CLD. HE is inconsistently associated with the presence of brain edema. Fibrous and protoplasmic astrocytes are differentially implicated in the pathogenesis of HE. The pathogenesis of HE is multifactorial causing an array of neurological symptoms.

show abstract

The neuronal and astrocytic protein SLC38A10 transports glutamine, glutamate, and aspartate, suggesting a role in neurotransmission

et al. 2017

View full text Add to dashboard Cite

In brain cells, glutamine transporters are vital to monitor and control the levels of glutamate and GABA . There are 11 members of the SLC 38 family of amino acid transporters of which eight have been functionally characterized. Here, we report the first histological and functional characterization of the previously orphan member, SLC 38A10. We used pairwise global sequence alignments to determine the sequence identity between the SLC 38 family members. SLC 38A10 was found to share 20–25% transmembrane sequence identity with several family members, and was predicted to have 11 transmembrane helices. SLC 38A10 immunostaining was abundant in mouse brain using a custom‐made anti‐ SLC 38A10 antibody and colocalization of SLC 38A10 immunoreactivity with markers for neurons and astrocytes was detected. Using Xenopus laevis oocytes overexpressing SLC 38A10, we show that SLC 38A10 mediates bidirectional transport of l ‐glutamine, l ‐alanine, l ‐glutamate, and d ‐aspartate, and efflux of l ‐serine. This profile mostly resembles system A members of the SLC 38 family. In conclusion, the bidirectional transport of glutamine, glutamate, and aspartate by SLC 38A10, and the immunostaining detected in neurons and astrocytes, suggest that SLC 38A10 plays a role in pathways involved in neurotransmission.

show abstract

Molecular Analysis of System N Suggests Novel Physiological Roles in Nitrogen Metabolism and Synaptic Transmission

Abstract: et al., 1983; Conti and Minelli, 1994). Since glia synthesize the glutamine used by neurons, this requires transfer of the amino acid between the two cell types (Ottersen et al., 1992). The role of glutamine in nitrogen metabolism and synaptic transmission thus involves

Cited by 302 publications

References 45 publications

Glutamine Uptake by Neurons: Interaction of Protons with System A Transporters

Glutamine Uptake by Neurons: Interaction of Protons with System A Transporters

Brain edema in acute liver failure and chronic liver disease: Similarities and differences

The neuronal and astrocytic protein SLC38A10 transports glutamine, glutamate, and aspartate, suggesting a role in neurotransmission

Contact Info

Product

Resources

About