Distinct synaptic localization patterns of brefeldin A-resistant guanine nucleotide exchange factors BRAG2 and BRAG3 in the mouse retina
Distinct synaptic localization patterns of brefeldin A-resistant guanine nucleotide exchange factors BRAG2 and BRAG3 in the mouse retina
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小鼠视网膜中布雷菲德菌素 A 抗性鸟嘌呤核苷酸交换因子 BRAG2 和 BRAG3 的独特突触定位模式
DOI：
10.1002/cne.23206
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Fukaya M
中科院分区：
文献类型：
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作者：
Sakagami H;Katsumata O;Hara Y;Tamaki H;Watanabe M;Harvey RJ;Fukaya M
BRAG/IQSEC是ADP核糖基化因子的鸟嘌呤核苷酸交换因子家族，其是调节膜运输和肌动蛋白细胞骨架的小GTP酶，并且包括由不同基因产生的三个结构相关成员（BRAG 1 -3）。在小鼠视网膜中，BRAG 1（也称为IQSEC 2）先前被证明定位于感光体末端的突触带，并与RIBEYE形成蛋白复合物。在这项研究中，我们研究了BRAG 2（IQSEC 1）和BRAG 3（IQSEC 3）在成年小鼠视网膜的光镜和电镜水平的免疫组织化学定位。在外网状层中，BRAG 2显示出与肌营养不良蛋白和β-肌营养不良蛋白聚糖密切相关的点状分布。免疫电镜分析显示，BRAG 2定位于视杆小球和视锥蒂的感光末梢的特定亚室。在内网状层中，BRAG 2和BRAG 3的免疫标记具有点状外观，提示突触标记。双重免疫染色显示BRAG 2优先与PSD-95和α-氨基-3-羟基-5-甲基-4-异恶唑丙酸酯型谷氨酸受体（AMPAR）共定位。相比之下，BRAG 3与桥蛋白和表达甘氨酸受体或γ-氨基丁酸A型受体（GABAAR）的抑制性突触亚群共定位。免疫电子显微镜分析显示，BRAG 2定位于双极二分体的突触后过程，而BRAG 3定位于传统突触的突触后成分。这些研究结果表明，BRAG/IQSEC家族成员在视网膜中不同的兴奋性和抑制性突触的功能和组织中具有关键作用。J. Comp.神经元521：860-876，2013。© 2012 Wiley Periodicals，Inc.
The BRAG/IQSEC is a family of guanine nucleotide exchange factors for ADP ribosylation factors, small GTPases that regulate membrane trafficking and actin cytoskeleton, and comprises three structurally related members (BRAG1–3) generated from different genes. In the mouse retina, BRAG1 (also known as IQSEC2) was previously shown to localize at synaptic ribbons of photoreceptor terminals and to form a protein complex with RIBEYE. In this study, we examined the immunohistochemical localization of BRAG2 (IQSEC1) and BRAG3 (IQSEC3) in the adult mouse retina at the light and electron microscopic levels. In the outer plexiform layer, BRAG2 showed a punctate distribution in intimate association with dystrophin and β‐dystroglycan. Immunoelectron microscopic analysis revealed that BRAG2 localized at specific subcompartments of photoreceptor terminals in both rod spherules and cone pedicles. In the inner plexiform layer, immunolabeling for both BRAG2 and BRAG3 had a punctate appearance, suggestive of synaptic labeling. Double immunostaining demonstrated that BRAG2 colocalized preferentially with PSD‐95 and α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionate‐type glutamate receptors (AMPARs). By contrast, BRAG3 colocalized with gephyrin and a subpopulation of inhibitory synapses expressing glycine receptors or γ‐aminobutyric acid type A receptors (GABAARs). Immunoelectron microscopic analysis revealed that BRAG2 localized to postsynaptic processes at bipolar dyads, while BRAG3 localized to postsynaptic components at conventional synapses. These findings suggest that BRAG/IQSEC family members have key roles in the function and organization of distinct excitatory and inhibitory synapses in the retina. J. Comp. Neurol. 521:860–876, 2013. © 2012 Wiley Periodicals, Inc.