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调控视网膜 Müller 细胞中谷氨酸水平的遗传途径。

Genetic pathways regulating glutamate levels in retinal Müller cells.

机构信息

Department of Ophthalmology, Hamilton Eye Institute, University of Tennessee Health Science Center, Memphis, TN 38163, USA.

出版信息

Neurochem Res. 2011 Apr;36(4):594-603. doi: 10.1007/s11064-010-0277-1. Epub 2010 Sep 30.

Abstract

Müller cells serve many functions including the regulation of extracellular glutamate levels. The product of two genes, Slc1a3 [aka solute carrier family 1 (glial high affinity glutamate transporter), member 3] and Glul (aka glutamine synthetase) are the primary role players that transport glutamate into the Müller cell and convert it into glutamine. In this study, we sought to identify the genetic regulation of both genes. Given their tightly coupled biological functions, we predicted that they would be similarly regulated. Using an array of 75 recombinant inbred strains of mice, we determined that Slc1a3 and Glul are differentially regulated by distinct chromosomal regions. Interestingly, despite their independent regulation, gene ontology analysis of tightly correlated genes reveals that the enriched and statistically significant molecular function categories of both directed acyclic graphs have substantial overlap, indicating that the shared functions of correlates of Slc1a3 and Glul include production and usage of ATP.

摘要

Müller 细胞具有多种功能,包括调节细胞外谷氨酸水平。两种基因的产物,Slc1a3(又名溶质载体家族 1(胶质高亲和力谷氨酸转运体)成员 3)和 Glul(又名谷氨酰胺合成酶),是将谷氨酸转运到 Müller 细胞并将其转化为谷氨酰胺的主要作用因子。在这项研究中,我们试图确定这两个基因的遗传调控。鉴于它们紧密偶联的生物学功能,我们预测它们会受到类似的调控。使用一系列 75 个重组近交系小鼠,我们确定 Slc1a3 和 Glul 由不同的染色体区域差异调控。有趣的是,尽管它们受到独立调控,但紧密相关基因的基因本体论分析表明,两个有向无环图的富集和统计学意义的分子功能类别有大量重叠,这表明 Slc1a3 和 Glul 的相关基因的共同功能包括生产和使用 ATP。

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