• 主题
高级搜索  >
历史搜索 清空历史
首页> 美国卫生研究院文献>PLoS Genetics >Kek-6: A truncated-Trk-like receptor for Drosophila neurotrophin 2 regulates structural synaptic plasticity
【2h】

Kek-6: A truncated-Trk-like receptor for Drosophila neurotrophin 2 regulates structural synaptic plasticity

机译：Kek-6：果蝇神经营养蛋白2的截断的Trk样受体调节结构性突触可塑性。

代理获取
本网站仅为用户提供外文OA文献查询和代理获取服务，本网站没有原文。下单后我们将采用程序或人工为您竭诚获取高质量的原文，但由于OA文献来源多样且变更频繁，仍可能出现获取不到、文献不完整或与标题不符等情况，如果获取不到我们将提供退款服务。请知悉。
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Neurotrophism, structural plasticity, learning and long-term memory in mammals critically depend on neurotrophins binding Trk receptors to activate tyrosine kinase (TyrK) signaling, but Drosophila lacks full-length Trks, raising the question of how these processes occur in the fly. Paradoxically, truncated Trk isoforms lacking the TyrK predominate in the adult human brain, but whether they have neuronal functions independently of full-length Trks is unknown. Drosophila has TyrK-less Trk-family receptors, encoded by the kekkon (kek) genes, suggesting that evolutionarily conserved functions for this receptor class may exist. Here, we asked whether Keks function together with Drosophila neurotrophins (DNTs) at the larval glutamatergic neuromuscular junction (NMJ). We tested the eleven LRR and Ig-containing (LIG) proteins encoded in the Drosophila genome for expression in the central nervous system (CNS) and potential interaction with DNTs. Kek-6 is expressed in the CNS, interacts genetically with DNTs and can bind DNT2 in signaling assays and co-immunoprecipitations. Ligand binding is promiscuous, as Kek-6 can also bind DNT1, and Kek-2 and Kek-5 can also bind DNT2. In vivo, Kek-6 is found presynaptically in motoneurons, and DNT2 is produced by the muscle to function as a retrograde factor at the NMJ. Kek-6 and DNT2 regulate NMJ growth and synaptic structure. Evidence indicates that Kek-6 does not antagonise the alternative DNT2 receptor Toll-6. Instead, Kek-6 and Toll-6 interact physically, and together regulate structural synaptic plasticity and homeostasis. Using pull-down assays, we identified and validated CaMKII and VAP33A as intracellular partners of Kek-6, and show that they regulate NMJ growth and active zone formation downstream of DNT2 and Kek-6. The synaptic functions of Kek-6 could be evolutionarily conserved. This raises the intriguing possibility that a novel mechanism of structural synaptic plasticity involving truncated Trk-family receptors independently of TyrK signaling may also operate in the human brain.
机译：哺乳动物的神经营养，结构可塑性，学习能力和长期记忆在很大程度上取决于神经营养蛋白与Trk受体的结合，从而激活酪氨酸激酶（TyrK）信号传导，但果蝇缺乏全长的Trk，这引发了这些过程如何实时发生的问题。矛盾的是，在成年人的大脑中，缺少TyrK的截短的Trk亚型占主导地位，但是它们是否具有独立于全长Trks的神经元功能尚不清楚。果蝇具有不含TyrK的Trk家族受体，由Kekkon（Kek）基因编码，表明该受体类可能存在进化上保守的功能。在这里，我们问Keks是否在幼虫谷氨酸能神经肌肉接头（NMJ）上与果蝇神经营养蛋白（DNT）一起起作用。我们测试了果蝇基因组中编码的11种LRR和含Ig（LIG）的蛋白质在中枢神经系统（CNS）中的表达以及与DNT的潜在相互作用。 Kek-6在中枢神经系统中表达，与DNT发生遗传相互作用，并可以在信号分析和免疫共沉淀中结合DNT2。配体结合是混杂的，因为Kek-6也可以结合DNT1，而Kek-2和Kek-5也可以结合DNT2。在体内，在运动神经元中突触地发现了Kek-6，而肌肉产生的DNT2在NMJ处起着逆行因子的作用。 Kek-6和DNT2调节NMJ生长和突触结构。有证据表明，Kek-6不能拮抗替代性DNT2受体Toll-6。相反，Kek-6和Toll-6在身体上相互作用，并共同调节结构突触的可塑性和体内平衡。使用下拉测定法，我们鉴定并验证了CaMKII和VAP33A作为Kek-6的细胞内伴侣，并显示它们调节DNT2和Kek-6下游的NMJ生长和活性区形成。 Kek-6的突触功能可以进化保守。这引起了一种有趣的可能性，即与TyrK信号传导无关的，涉及截短的Trk家族受体的结构性突触可塑性的新机制也可以在人脑中发挥作用。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
代理获取

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号