Chaudhry Farrukh A, Schmitz Dietmar, Reimer Richard J, Larsson Peter, Gray Andrew T, Nicoll Roger, Kavanaugh Michael, Edwards Robert H
Department of Neurology, University of California San Francisco School of Medicine, San Francisco, California 94143-0435, USA.
J Neurosci. 2002 Jan 1;22(1):62-72. doi: 10.1523/JNEUROSCI.22-01-00062.2002.
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+ for Na+ and neutral amino acid catalyzed by SN1, we now show that SA1 and SA2 do not couple H+ 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+ thus contribute to the delivery of glutamine from glia to neurons. Nonetheless, although they are not transported, H+ inhibit SA1 and SA2 by competing with Na+.
星形胶质细胞为神经元提供合成谷氨酸和γ-氨基丁酸所需的谷氨酰胺。然而，从胶质细胞向神经元转运谷氨酰胺所涉及的机制仍知之甚少。最近的研究表明，系统N转运体SN1参与星形胶质细胞释放谷氨酰胺，而与之密切相关的系统A转运体SA1和SA2则参与神经元摄取谷氨酰胺。为了了解这些密切相关的蛋白质如何介导不同方向的通量，我们研究了它们的离子偶联。与SN1催化的H⁺与Na⁺及中性氨基酸的电中性交换不同，我们现在发现SA1和SA2不会将H⁺移动与氨基酸通量偶联。因此，SA1和SA2是生电性的，不像SN1那样容易介导通量逆转。系统N和A转运体在与H⁺偶联方面的差异有助于将谷氨酰胺从胶质细胞输送到神经元。尽管如此，虽然H⁺不被转运，但它们通过与Na⁺竞争来抑制SA1和SA2。
