A-Kinase-Anchoring Protein (AKAP150) is expressed in Astrocytes and Upregulated in Response to Ischemia.
A-Kinase-Anchoring Protein (AKAP150) is expressed in Astrocytes and Upregulated in Response to Ischemia.
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DOI：
10.1016/j.neuroscience.2018.05.019
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发表时间：
2018-08-01
期刊：
影响因子：
3.3
通讯作者：
Eaton MJ
中科院分区：
文献类型：
--
作者：
Rivera-Pagán AF;Méndez-González MP;Rivera-Aponte DE;Malpica-Nieves CJ;Melnik-Martínez KV;Zayas-Santiago A;Maldonado-Martínez G;Shuba YM;Skatchkov SN;Eaton MJ
A-激酶锚定蛋白(AKAPs)是一种支架蛋白，与激酶和磷酸酶相关联，并将它们定向到特定的亚膜位置来协调信号事件。AKAP150是人类AKAP79在啮齿动物中的同源基因，在神经元中得到了广泛的研究，但对AKAP150在脑中主要细胞类型星形胶质细胞中的定位和功能知之甚少。因此，在这项研究中，我们评估了AKAP150在星形胶质细胞中的定位，并阐明了它在生理和缺血条件下的作用。在此，我们证明了AKAP150定位于星形胶质细胞，并在体外和体内缺血时上调。RNAi下调AKAP150使星形胶质细胞膜电位去极化，并使星形胶质细胞在缺血条件下摄取细胞外钾的能力显著降低80%。因此，脑缺血时AKAP150的上调保留了星形胶质细胞的钾电导和相关的超极化膜电位；星形胶质细胞的特性是维持细胞外脑内平衡所必需的。综上所述，这些数据表明，AKAP150可能在病理条件下星形胶质细胞的神经保护机制中发挥关键作用。
A-kinase anchoring proteins, AKAPs, are scaffolding proteins that associate with kinases and phosphatases, and direct them to a specific submembrane site to coordinate signaling events. AKAP150, a rodent ortholog of human AKAP79, has been extensively studied in neurons, but very little is known about the localization and function of AKAP150 in astrocytes, the major cell type in brain. Thus, in this study, we assessed the localization of AKAP150 in astrocytes and elucidated its role during physiological and ischemic conditions. Herein, we demonstrate that AKAP150 is localized in astrocytes and is up-regulated during ischemia both in vitro and in vivo. Knock-down of AKAP150 by RNAi depolarizes the astrocytic membrane potential and substantially reduces by 80% the ability of astrocytes to take up extracellular potassium during ischemic conditions. Therefore, upregulation of AKAP150 during ischemia preserves potassium conductance and the associated hyperpolarized membrane potential of astrocytes; properties of astrocytes needed to maintain extracellular brain homeostasis. Taken together, these data suggest that AKAP150 may play a pivotal role in the neuroprotective mechanism of astrocytes during pathological conditions.
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