Expression Analysis of Zinc Transporters in Nervous Tissue Cells Reveals Neuronal and Synaptic Localization of ZIP4.
Expression Analysis of Zinc Transporters in Nervous Tissue Cells Reveals Neuronal and Synaptic Localization of ZIP4.
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DOI：
10.3390/ijms22094511
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发表时间：
2021-04-26
影响因子：
5.6
通讯作者：
Grabrucker AM
中科院分区：
文献类型：
--
作者：
De Benedictis CA;Haffke C;Hagmeyer S;Sauer AK;Grabrucker AM
近年来，研究表明锌离子在大脑功能的生理学中发挥着重要作用。锌作为一种有效的神经调节剂和信号离子，调节健康的大脑发育以及神经元和神经胶质细胞的功能。因此，大脑及其细胞内锌的浓度受到严格控制。锌转运蛋白是（外）细胞锌水平的关键调节因子，锌稳态和锌转运蛋白的失调与神经退行性和神经精神疾病有关。然而，迄今为止，特定家庭成员的存在及其在脑细胞内的亚细胞定位尚未得到详细研究。在这里，我们分析了大鼠大脑中所有锌转运蛋白 (ZnT) 和 Irt 样蛋白 (ZIP) 的表达。我们进一步使用原代大鼠神经元和大鼠星形胶质细胞系来区分神经元或星形胶质细胞或两者中发现的表达。我们发现 ZIP4 在星形胶质细胞中表达，但在神经元中表达量明显更高，这一发现以前从未报道过。在神经元中，ZIP4 定位于突触，并与兴奋性突触的主要突触后支架蛋白形成复合物。突触 ZIP4 对局部锌水平的短期波动做出反应。我们得出结论，ZIP4 可能在兴奋性突触后具有迄今为止尚未描述的功能作用。
In the last years, research has shown that zinc ions play an essential role in the physiology of brain function. Zinc acts as a potent neuromodulatory agent and signaling ions, regulating healthy brain development and the function of both neurons and glial cells. Therefore, the concentration of zinc within the brain and its cells is tightly controlled. Zinc transporters are key regulators of (extra-) cellular zinc levels, and deregulation of zinc homeostasis and zinc transporters has been associated with neurodegenerative and neuropsychiatric disorders. However, to date, the presence of specific family members and their subcellular localization within brain cells have not been investigated in detail. Here, we analyzed the expression of all zinc transporters (ZnTs) and Irt-like proteins (ZIPs) in the rat brain. We further used primary rat neurons and rat astrocyte cell lines to differentiate between the expression found in neurons or astrocytes or both. We identified ZIP4 expressed in astrocytes but significantly more so in neurons, a finding that has not been reported previously. In neurons, ZIP4 is localized to synapses and found in a complex with major postsynaptic scaffold proteins of excitatory synapses. Synaptic ZIP4 reacts to short-term fluctuations in local zinc levels. We conclude that ZIP4 may have a so-far undescribed functional role at excitatory postsynapses.
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影响因子：
3.7
作者：
Bosomworth HJ;Adlard PA;Ford D;Valentine RA
通讯作者：
Valentine RA
DOI：
10.1073/pnas.1222142110
发表时间：
2013-06-11
影响因子：
11.1
作者：
Chowanadisai, Winyoo;Graham, David M.;Messerli, Mark A.
通讯作者：
Messerli, Mark A.
影响因子：
3.4
作者：
Colvin, Robert A.;Lai, Barry;Lee, Daewoo
通讯作者：
Lee, Daewoo
影响因子：
4
作者：
Beyer, Nancy;Coulson, David T. R.;Johnston, Janet A.
通讯作者：
Johnston, Janet A.
影响因子：
14.5
作者：
Grabrucker, Stefanie;Jannetti, Linda;Grabrucker, Andreas M.
通讯作者：
Grabrucker, Andreas M.