Cloning of an Amino Acid Transporter with Functional Characteristics and Tissue Expression Pattern Identical to That of System A

Sugawara, Mitsuru; Nakanishi, Takeo; Fei, You-Jun; Huang, Wei; Ganapathy, Malliga E.; Leibach, Frederick H.; Ganapathy, Vadivel

doi:10.1074/jbc.c000205200

Cited by 244 publications

(183 citation statements)

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“…Expression of SA2 using a vaccinia virus-T7 polymerase system confers increased uptake of 3 H-MeAIB relative to untransfected cells (Fig. 2a), as previously reported for SA2 and SA1 (Reimer et al, 2000;Sugawara et al, 2000;Yao et al, 2000). MeAIB saturates transport by SA2 with a K m 1.6 Ϯ 0.33 mM, n ϭ 3 (Fig.…”

Section: Electrogenic Transport and Coupled Currentssupporting

confidence: 79%

“…MeAIB saturates transport by SA2 with a K m 1.6 Ϯ 0.33 mM, n ϭ 3 (Fig. 2b), substantially higher than the 0.15-0.5 mM K m reported for SA1 (Reimer et al, 2000;Sugawara et al, 2000;Yao et al, 2000). Very similar to SA1, MeAIB flux mediated by SA2 tolerates substitution of Na ϩ by Li ϩ but not choline and replacement of chloride by thiocyanate (Fig.…”

Section: Electrogenic Transport and Coupled Currentsmentioning

confidence: 75%

“…1 A) might contribute to other aspects of the glutamineglutamate cycle, such as the uptake of glutamine by neurons. SA1 transports glutamine and resides on neurons as well as astrocytes (Reimer et al, 2000;Sugawara et al, 2000). However, SA1 recognizes other neutral amino acids with equal or greater affinity than glutamine and appears in virtually all cells.…”

Section: Resultsmentioning

confidence: 99%

“…We have recently found that the currents associated with SN1 are largely if not entirely uncoupled from transport (F. A. Chaudhry, M. Kavanaugh, and R. H. Edwards, unpublished observations), raising the possibility that currents associated with closely related System A transporters are also uncoupled (Reimer et al, 2000;Sugawara et al, 2000;Varoqui et al, 2000;Yao et al, 2000). To reassess the relationship of currents to transport by both SA1 and SA2, we first measured uptake of the prototypic System A substrate 3 H-MeAIB.…”

Section: Electrogenic Transport and Coupled Currentsmentioning

confidence: 99%

“…Together with its expression on astrocytes, these observations suggest that SN1 confers the efflux of glutamine from glia required to sustain the glutamineglutamate cycle. SN1 also shows strong sequence similarity to the proteins responsible for another classical amino acid transport system, System A (Reimer et al, 2000;Sugawara et al, 2000;Varoqui et al, 2000;Yao et al, 2000).…”

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confidence: 99%

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

et al. 2002

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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 .

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Section: Electrogenic Transport and Coupled Currentssupporting

confidence: 79%

Section: Electrogenic Transport and Coupled Currentsmentioning

confidence: 75%

Section: Resultsmentioning

confidence: 99%

Section: Electrogenic Transport and Coupled Currentsmentioning

confidence: 99%

mentioning

confidence: 99%

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

et al. 2002

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Amino Acid Transport Across the Mammalian Intestine

Bröer

Fairweather

2018

Comprehensive Physiology

118

110

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The small intestine mediates the absorption of amino acids after ingestion of protein and sustains the supply of amino acids to all tissues. The small intestine is an important contributor to plasma amino acid homeostasis, while amino acid transport in the large intestine is more relevant for bacterial metabolites and fluid secretion. A number of rare inherited disorders have contributed to the identification of amino acid transporters in epithelial cells of the small intestine, in particular cystinuria, lysinuric protein intolerance, Hartnup disorder, iminoglycinuria, and dicarboxylic aminoaciduria. These are most readily detected by analysis of urine amino acids, but typically also affect intestinal transport. The genes underlying these disorders have all been identified. The remaining transporters were identified through molecular cloning techniques to the extent that a comprehensive portrait of functional cooperation among transporters of intestinal epithelial cells is now available for both the basolateral and apical membranes. Mouse models of most intestinal transporters illustrate their contribution to amino acid homeostasis and systemic physiology. Intestinal amino acid transport activities can vary between species, but these can now be explained as differences of amino acid transporter distribution along the intestine. © 2019 American Physiological Society. Compr Physiol 9:343‐373, 2019.

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Highly differential expression of SN1, a bidirectional glutamine transporter, in astroglia and endothelium in the developing rat brain

Boulland¹,

Rafiki²,

Levy³

et al. 2003

Glia

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The transmitters glutamate and GABA also subserve trophic action and are required for normal development of the brain. They are formed from glutamine, which may be synthesized in glia or extracted from the blood. In the adult, the glutamine transporter SN1 is expressed in the astroglia. SN1 works in both directions, depending on the concentration gradients of its substrates and cotransported ions, and is thought to regulate extracellular glutamine and to supply the neurons with the transmitter precursor. In this article, we have quantified the expression and studied the localization of SN1 at different developmental stages. SN1 is expressed in astroglia throughout the CNS from embryonic stages through adulthood. No indication of SN1 staining in neuronal elements has been obtained at any stage. Quantitative immunoblotting of whole brain extracts demonstrates increasing expression of SN1 from P0, reaching a peak at P14, twice the adult level. A moderate and slower rise and fall of the expression levels of SN1 occurs in the cerebellum. Strong transient SN1-like staining is also found in Bergmann glia and vascular endothelium in the first postnatal weeks. Strong intracellular staining in the same time period suggests a high rate of SN1 synthesis in the early postnatal period. This coincides with the increasing levels of glutamate and GABA in the CNS and with the time course of synaptogenesis. This study suggests that the expression of SN1 is highly regulated, correlating with the demand for glutamine during the critical period of development.

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Cloning of an Amino Acid Transporter with Functional Characteristics and Tissue Expression Pattern Identical to That of System A

Cited by 244 publications

References 20 publications

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

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

Amino Acid Transport Across the Mammalian Intestine

Highly differential expression of SN1, a bidirectional glutamine transporter, in astroglia and endothelium in the developing rat brain

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