更新于：2024-05-01

GluK5

glutamate ionotropic receptor kainate type subunit 5

更新于：2024-05-01

基本信息

别名

EAA2、Excitatory amino acid receptor 2、GluK5

+ [7]

简介

Receptor for glutamate. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. The postsynaptic actions of Glu are mediated by a variety of receptors that are named according to their selective agonists. This receptor binds kainate > quisqualate > domoate > L-glutamate >> AMPA >> NMDA = 1S,3R-ACPD.

关联

100 项与 GluK5 相关的临床结果

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100 项与 GluK5 相关的转化医学

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0 项与 GluK5 相关的专利（医药）

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279

项与 GluK5 相关的文献（医药）

2024-02-24·Scientific reports

Behavioral analysis of kainate receptor KO mice and the role of GluK3 subunit in anxiety.

Article

作者: Izumi Iida ; Kohtarou Konno ; Rie Natsume ; Manabu Abe ; Masahiko Watanabe ; Kenji Sakimura ; Miho Terunuma

Kainate receptors (KARs) are one of the ionotropic glutamate receptors in the central nervous system (CNS) comprised of five subunits, GluK1-GluK5. There is a growing interest in the association between KARs and psychiatric disorders, and there have been several studies investigating the behavioral phenotypes of KAR deficient mice, however, the difference in the genetic background has been found to affect phenotype in multiple mouse models of human diseases. Here, we examined GluK1-5 single KO mice in a pure C57BL/6N background and identified that GluK3 KO mice specifically express anxiolytic-like behavior with an alteration in dopamine D2 receptor (D2R)-induced anxiety, and reduced D2R expression in the striatum. Biochemical studies in the mouse cortex confirmed that GluK3 subunits do not assemble with GluK4 and GluK5 subunits, that can be activated by lower concentration of agonists. Overall, we found that GluK3-containing KARs function to express anxiety, which may represent promising anti-anxiety medication targets.

2023-11-15·BMC genomics

Changes in ADAR RNA editing patterns in CMV and ZIKV congenital infections.

Article

作者: Benjamin Wales-McGrath ; Heather Mercer ; Helen Piontkivska

BACKGROUND:

RNA editing is a process that increases transcriptome diversity, often through Adenosine Deaminases Acting on RNA (ADARs) that catalyze the deamination of adenosine to inosine. ADAR editing plays an important role in regulating brain function and immune activation, and is dynamically regulated during brain development. Additionally, the ADAR1 p150 isoform is induced by interferons in viral infection and plays a role in antiviral immune response. However, the question of how virus-induced ADAR expression affects host transcriptome editing remains largely unanswered. This question is particularly relevant in the context of congenital infections, given the dynamic regulation of ADAR editing during brain development, the importance of this editing for brain function, and subsequent neurological symptoms of such infections, including microcephaly, sensory issues, and other neurodevelopmental abnormalities. Here, we begin to address this question, examining ADAR expression in publicly available datasets of congenital infections of human cytomegalovirus (HCMV) microarray expression data, as well as mouse cytomegalovirus (MCMV) and mouse/ human induced pluripotent neuroprogenitor stem cell (hiNPC) Zika virus (ZIKV) RNA-seq data.

RESULTS:

We found that in all three datasets, ADAR1 was overexpressed in infected samples compared to uninfected samples. In the RNA-seq datasets, editing rates were also analyzed. In all mouse infections cases, the number of editing sites was significantly increased in infected samples, albeit this was not the case for hiNPC ZIKV samples. Mouse ZIKV samples showed altered editing of well-established protein-recoding sites such as Gria3, Grik5, and Nova1, as well as editing sites that may impact miRNA binding.

CONCLUSIONS:

Our findings provide evidence for changes in ADAR expression and subsequent dysregulation of ADAR editing of host transcriptomes in congenital infections. These changes in editing patterns of key neural genes have potential significance in the development of neurological symptoms, thus contributing to neurodevelopmental abnormalities. Further experiments should be performed to explore the full range of editing changes that occur in different congenital infections, and to confirm the specific functional consequences of these editing changes.

2023-08-01·Proteins

Partial agonism in heteromeric GLUK2/GLUK5 kainate receptor.

Article

作者: Nabina Paudyal ; Anindita Das ; Elisa Carrillo ; Vladimir Berka ; Vasanthi Jayaraman

Kainate receptors are a subtype of ionotropic glutamate receptors that form transmembrane channels upon binding glutamate. Here, we have investigated the mechanism of partial agonism in heteromeric GluK2/K5 receptors, where the GluK2 and GluK5 subunits have distinct agonist binding profiles. Using single-molecule Förster resonance energy transfer, we found that at the bi-lobed agonist-binding domain, the partial agonist AMPA-bound receptor occupied intermediate cleft closure conformational states at the GluK2 cleft, compared to the more open cleft conformations in apo form and more closed cleft conformations in the full agonist glutamate-bound form. In contrast, there is no significant difference in cleft closure states at the GluK5 agonist-binding domain between the partial agonist AMPA- and full agonist glutamate-bound states. Additionally, unlike the glutamate-bound state, the dimer interface at the agonist-binding domain is not decoupled in the AMPA-bound state. Our findings suggest that partial agonism observed with AMPA binding is mediated primarily due to differences in the GluK2 subunit, highlighting the distinct contributions of the subunits towards activation.

项与 GluK5 相关的新闻（医药）

2022-11-22

·生物制品圈

降糖赛道：分子互作技术助您笑傲江湖

这两年集采“灵魂砍价”的新闻频频出现，特别是在胰岛素领域尤为突出。据估算，2021年全国胰岛素集采量2.1亿支，涉及金额170亿，中选产品价格平均降幅 48%。胰岛素集采对于药企而言，喜忧参半。喜的是，集采后中外企业的市场格局会发生变化，有利于推进中选企业降低生产成本和新药研发，推动产业优化升级。忧的是，短期内股价下降，营收数字下滑，集采阵痛明显。此刻，对于药企而言，研发出质优价廉的产品成为当务之急。今天，我们就通过赛诺菲研发Insulin aspart Sanofi剑指诺和诺德NovoRapid的案例，看分子互作“金标准”的Biacore如何助你在降糖赛道笑傲江湖。胰岛素领域的头把交椅一直被诺和诺德占据，NovoRapid更是业界明星产品。2020年，欧盟委员会批准Insulin aspart Sanofi上市，这对NovoRapid产生巨大挑战。SAR341402（Insulin aspart Sanofi）是由赛诺菲公司研发，以NovoRapid为原型药，经EMA批准上市的胰岛素类似药。SAR341402是利用重组DNA技术由非致病性大肠杆菌产生的速效胰岛素，其与人胰岛素同源，唯一的不同点在于将人胰岛素氨基酸链 B28 位的脯氨酸替换为天门冬氨酸。正是由于此修饰使得门冬胰岛素通过电荷排斥效应阻止胰岛素自我聚合，从而达到起效快、活性高的特点。在SAR341402申报报告中，与受体的结合活性测定是药效学研究的重点。面对众多分子互作的检测技术，研究人员最终选择了Biacore SPR技术，理由很简单：快速、实时、直接的检测方法受到研究人员的认可（在讲究内容精简的药物申报报告中，点出Biacore SPR技术具备的三大优势，着实可见研究人员对于Biacore的喜爱）。在检测实验中，研究人员首先将胰岛素受体IR-A 或 IR-B偶联在Biacore传感芯片上。随后，将SAR341402 （四个批次）、参考药物（NovoLog、NovoRapi 各三批）在特定浓度范围内进行检测，每批次药物重复6次实验。四个检测数据（ka1, kd1, ka2, kd2）分别拟合计算，同时计算每个药物对应的加权几何平均值，并且获得对应95%置信区间（见下表）。获得上述数据后，再对三个药物进行两两对比，获取比值及对应90%置信区间（见下表）。针对于结合和解离速率常数 ka1、ka2、kd1、kd2，平均结合和解离速率常数比值的90%置信区间落在 0.70 - 1.43 接受度范围内，表明了SAR341402与参考药物在胰岛素受体IR-A 、 IR-B的结合动力学数据上是相似的。随后，研究人员再将IGF-1受体偶联在Biacore传感芯片上，按照与胰岛素受体相似的检测方法进行检测，拟合计算获得四个检测数据（ka1, kd1, ka2, kd2），同时计算每个药物对应的加权几何平均值，并且获得对应95%置信区间（见下表）。获得上述数据后，再对三个药物进行两两对比，获取比值及对应90%置信区间（见下表）。针对于结合和解离速率常数 ka1、ka2、kd1 和 kd2，平均结合和解离速率常数比值的90%置信区间落在 0.70 - 1.43 接受度范围内，表明了SAR341402与参考药物在IGF-1受体的结合动力学数据上也是相似的。对于上述实验数据，可能有些小伙伴会疑问：这些数据到底表现出Biacore哪些惊艳的特点？作者认为可以用一句话概括：高数据质量下的高通量检测与大数据分析能力。首先，两位点结合模型，三药物直接对比，十批次药物检测，一百八十组数据分析，这都表现出Biacore具备多样的结合模型分析模块，高通量检测速度，大数据分析处理能力。此外，如此亮眼的CV数据更是让人惊艳于Biacore的整体数据质量。这么大样本，低CV值的数据结果，就要求仪器检测精度与稳定性必须非常高。作为行业的金标准，Biacore检测精度与检测稳定性是市面其他设备无法相提并论的，其次，千分之一度的温控精度保障了检测温度敏感型样品的刚性需求，而且，样品板封膜与钢针穿刺取样的设计保证了整个检测过程中样品浓度始终不变，保证无论检测时间长或短，样品顺序前或后，数据重复性超高的效果。也就是因为Biacore如此优异的表现，助力了赛诺菲Insulin aspart Sanofi的上市。向来枉费推移力,此日中流自在行。在如今竞争激烈的降糖赛道，Biacore将通过“金标准”的品质，助力药企研发更优的产品，让患者少花钱用好药，让企业面对竞争，从容应对，笑傲江湖。Biacore一直致力于用创新技术，拓展研究领域，提高研发效率，加速生物疗法，基于用户需求不断改进非标记生物分子相互作用分析系统，更好地为基础科研、药物研发开创未来。肩负这一使命，我们终于迎来了新一代SPR系统——Biacore™ 1 系列，在此诚邀每一位关注Biacore的您加入我们，在云端共同见证Biacore™ 1 系列的诞生，与行业大咖一同探索分子互作前沿进展，揭幕下一代分子相互作用研究的新浪潮！2022.11.24敬请期待，不见不散！参考文献：Assessment report EMA/CHMP/269410/2020识别微信二维码，添加生物制品圈小编，符合条件者即可加入生物制品微信群！请注明：姓名+研究方向！版权声明本公众号所有转载文章系出于传递更多信息之目的，且明确注明来源和作者，不希望被转载的媒体或个人可与我们联系(cbplib@163.com)，我们将立即进行删除处理。所有文章仅代表作者观点，不代表本站立场。

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