Abnormal glycosylation of EAAT1 and EAAT2 in prefrontal cortex of elderly patients with schizophrenia.

Abnormal glycosylation of EAAT1 and EAAT2 in prefrontal cortex of elderly patients with schizophrenia.
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DOI:
10.1016/j.schres.2009.07.025
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发表时间:
2010-03
影响因子:
4.5
通讯作者:
McCullumsmith, Robert E.
McCullumsmith, Robert E.
中科院分区:
医学2区
文献类型:
--
作者:
Bauer, Deborah;Haroutunian, Vahram;Meador-Woodruff, James H.;McCullumsmith, Robert E.

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兴奋性氨基酸转运蛋白(EAAT)是调节突触谷氨酸水平所必需的分子家族。EAAT还可能受到N-糖基化的调节,N-糖基化是一种翻译后修饰,对于许多细胞功能(包括在质膜中的定位)至关重要。我们假设EAAT的糖基化在精神分裂症中是异常的。为了验证这一假设,我们处理了精神分裂症患者和去糖基化酶对照组的背外侧前额叶和前扣带皮层的死后组织。然后,我们使用蛋白质印迹分析测量EAAT分子量的变化,以确定从转运蛋白裂解的聚糖的质量。我们发现了精神分裂症患者EAAT 1和EAAT 2糖基化程度较低的证据。我们没有检测到N-连接的糖基化EAAT 3在精神分裂症或在这些地区的比较对象。我们的数据表明,精神分裂症患者谷氨酸转运体的翻译后修饰异常,表明谷氨酸再摄取能力降低。
The excitatory amino acid transporters (EAATs) are a family of molecules that are essential for regulation of synaptic glutamate levels. The EAATs may also be regulated by N-glycosylation, a posttranslational modification that is critical for many cellular functions including localization in the plasma membrane. We hypothesized that glycosylation of the EAATs is abnormal in schizophrenia. To test this hypothesis, we treated postmortem tissue from the dorsolateral prefrontal and anterior cingulate cortices of patients with schizophrenia and comparison subjects with deglycosylating enzymes. We then measured the resulting shifts in molecular weight of the EAATs using Western blot analysis to determine the mass of glycans cleaved from the transporter. We found evidence for less glycosylation of both EAAT1 and EAAT2 in schizophrenia. We did not detect N-linked glycosylation of EAAT3 in either schizophrenia or the comparison subjects in these regions. Our data suggest an abnormality of posttranslational modification of glutamate transporters in schizophrenia that suggests a decreased capacity for glutamate reuptake.
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