Sodium-dependent vitamin C transporter-2 mediates vitamin C transport at the cortical nerve terminal.
Sodium-dependent vitamin C transporter-2 mediates vitamin C transport at the cortical nerve terminal.
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DOI：
10.1002/jnr.23669
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发表时间：
2015-12
影响因子：
4.2
通讯作者：
May JM
中科院分区：
文献类型：
--
作者：
Pierce MR;Raj A;Betke KM;Zeidan LN;Matthies HJ;May JM
维生素C（VC）在突触终扣处被转运，但这是如何发生的尚未阐明。在这项研究中，我们研究了钠依赖性维生素C转运蛋白2（SVCT 2）在皮质神经末梢转运VC中的作用。培养的小鼠上级颈神经节细胞的免疫染色显示SVCT 2在突触前终扣中表达，与囊泡单胺转运体2和去甲肾上腺素转运体共定位。丰富的皮质突触体的免疫印迹表明，SVCT 2是丰富的突触前馏分，确认一个主要的突触前位置。在粗突触体中，已知的SVCT 2抑制剂抑制VC的摄取。此外，VC摄取的动力学特征与SVCT 2介导的功能一致。VC也被发现从突触体流出的机制不涉及SVCT2。事实上，VC外排实质上被SVCT 2上的VC再摄取所抵消。SVCT 2在突触前神经末梢的存在和功能表明，它是负责恢复释放到突触间隙中的VC的转运蛋白。在培养的小鼠上级颈神经节细胞的突触前终扣中，维生素C（VC）转运蛋白SVCT 2与囊泡单胺转运蛋白2和去甲肾上腺素转运蛋白共定位。SVCT 2在皮质突触体中也有功能，这表明它负责恢复释放到突触间隙中的VC。
It has been shown that vitamin C (VC) is transported at synaptic boutons, but how this occurs has not been elucidated. In this study, we investigated the role of the sodium-dependent vitamin C transporter-2 (SVCT2) in transporting VC at the cortical nerve terminal. Immunostaining of cultured mouse superior cervical ganglion cells showed the SVCT2 to be expressed in presynaptic boutons, co-localizing with the vesicular monoamine transporter-2 and the norepinephrine transporter. Immunoblotting of enriched cortical synaptosomes demonstrated that the SVCT2 was enriched in presynaptic fractions, confirming a predominant presynaptic location. In crude synaptosomes, known inhibitors of SVCT2 inhibited uptake of VC. Further, the kinetic features of VC uptake were consistent with SVCT2-mediated function. VC was also found to efflux from synaptosomes by a mechanism not involving the SVCT2. Indeed, VC efflux was substantially offset by re-uptake of VC on the SVCT2. The presence and function of the SVCT2 at the presynaptic nerve terminal suggest that it is the transporter responsible for recovery of VC released into the synaptic cleft. The vitamin C (VC) transporter, SVCT2, co-localizes with the vesicular monoamine transporter-2 and the norepinephrine transporter in the presynaptic boutons of cultured mouse superior cervical ganglion cells. The SVCT2 is also functional in cortical synaptosomes suggesting that it is responsible for the recovery of VC released into the synaptic cleft.