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囊泡 GABA 转运体 (VGAT) 转运 β-丙氨酸。

Vesicular GABA transporter (VGAT) transports β-alanine.

机构信息

Advanced Research Center, Okayama University, Okayama, Japan.

出版信息

J Neurochem. 2013 Nov;127(4):482-6. doi: 10.1111/jnc.12393. Epub 2013 Aug 27.

Abstract

Vesicular GABA transporter (VGAT) is expressed in GABAergic and glycinergic neurons, and is responsible for vesicular storage and subsequent exocytosis of these inhibitory amino acids. In this study, we show that VGAT recognizes β-alanine as a substrate. Proteoliposomes containing purified VGAT transport β-alanine using Δψ but not ΔpH as a driving force. The Δψ-driven β-alanine uptake requires Cl(-). VGAT also facilitates Cl(-) uptake in the presence of β-alanine. A previously described VGAT mutant (Glu213Ala) that disrupts GABA and glycine transport similarly abrogates β-alanine uptake. These findings indicated that VGAT transports β-alanine through a mechanism similar to those for GABA and glycine, and functions as a vesicular β-alanine transporter. Vesicular GABA transporter (VGAT) is expressed in GABAergic and glycinergic neurons, and is responsible for vesicular storage and subsequent exocytosis of these inhibitory amino acids. In the present study, we showed that proteoliposomes containing purified VGAT transport β-alanine using Δψ as a driving force. VGAT also facilitates Cl(-) uptake. Our findings indicated that VGAT functions as a vesicular β-alanine transporter.

摘要

囊泡 GABA 转运体 (VGAT) 在 GABA 能和甘氨酸能神经元中表达,负责这些抑制性氨基酸的囊泡储存和随后的胞吐。在这项研究中,我们表明 VGAT 可识别 β-丙氨酸作为底物。含有纯化 VGAT 的脂质体使用 Δψ 而非 ΔpH 作为驱动力来转运 β-丙氨酸。Δψ 驱动的 β-丙氨酸摄取需要 Cl(-)。VGAT 还在存在 β-丙氨酸的情况下促进 Cl(-)摄取。先前描述的一种 VGAT 突变体(Glu213Ala),它破坏 GABA 和甘氨酸的转运,同样使 β-丙氨酸摄取失活。这些发现表明,VGAT 通过类似于 GABA 和甘氨酸的机制转运 β-丙氨酸,并作为囊泡 β-丙氨酸转运体发挥作用。囊泡 GABA 转运体 (VGAT) 在 GABA 能和甘氨酸能神经元中表达,负责这些抑制性氨基酸的囊泡储存和随后的胞吐。在本研究中,我们表明含有纯化 VGAT 的脂质体使用 Δψ 作为驱动力来转运 β-丙氨酸。VGAT 还促进 Cl(-)摄取。我们的发现表明 VGAT 作为囊泡 β-丙氨酸转运体发挥作用。

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