Analyzing the Complexins of the photoreceptor ribbon synapses in mouse retina

分析小鼠视网膜感光带突触的复合蛋白

• 批准号: 428863786
• 负责人: Professor Dr. Johann Helmut Brandstätter
• 金额: --
• 依托单位: Abteilung Molekulare Neurobiologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2019
• 资助国家: 德国
• 起止时间: 2018-12-31 至 2021-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/428863786?language=en
• 关键词: Analyzing; Complexins; photoreceptor; ribbon; synapses

The Complexins (Cplxs) 1 and 2 are high affinity SNARE-interacting proteins. They regulate a late step in the synaptic vesicle fusion reaction with the plasma membrane, most likely by stabilizing the SNARE complex in order to maintain synaptic vesicles in a release competent state. Different from the Cplxs 1 and 2 are the Cplxs 3 and 4. They show limited homology to the Cplxs 1 and 2, possess a C-terminal CAAX-box motif for membrane interaction and are predominantly expressed at ribbon synapses of the vertebrate retina. From a previous study examining Cplx 3/4 double-knockout mice, we know that the Cplxs 3 and 4 have diverse functions in neurotransmitter release from photoreceptor ribbon synapses: they suppress tonic and facilitate evoked release, and they play a putative role in the adaptation-dependent regulation of the availability of ribbon-tethered releasable synaptic vesicles. However, the most fundamental question in the field has not been approached so far: what are the underlying molecular and cell biological mechanisms of retinal Cplx function? To address this question, we will study the adaptation-dependent expression (RNA, protein) of the Cplxs 3 and 4, and their switching between soluble and insoluble (membrane-associated) forms, which may depend on farnesylation of their unique C terminus. Moreover, we will search for interaction partners, which may influence the cell biology of the Cplxs 3 and 4 in general and their functional availability in particular (regulators), and which may modulate downstream Cplx functions and thereby transmitter release in an activity-dependent manner (effectors).

复合蛋白（CPLXS）1和2是高亲和力圈圈蛋白。他们调节与质膜突触囊泡融合反应的后期步骤，最有可能是通过稳定SNARE复合物以将突触囊泡维持在释放能力的状态中。与CPLXS 1和2不同的是CPLXS 3和4。它们与CPLXS 1和2的同源性有限，具有用于膜相互作用的C端Caax-box基序，并且主要在椎骨视网膜的带状突触下表达。从先前研究CPLX 3/4双 - 敲击小鼠的研究中，我们知道CPLXS 3和4在神经递质中从光感受器丝带突触中释放出多种功能：它们抑制滋补和促进唤起的释放，并且它们在适应性依赖于核糖核定的辅助式合成的调节中起着推定的作用。但是，到目前为止，该领域最基本的问题尚未解决：视网膜CPLX功能的基本分子和细胞生物学机制是什么？为了解决这个问题，我们将研究CPLXS 3和4的适应性依赖性表达（RNA，蛋白质），以及它们在可溶性和不溶性和不溶性（膜相关）形式之间的切换，这可能取决于其独特的C末端的Farnesylation。此外，我们将搜索相互作用伙伴，这可能会影响CPLXS 3和4的细胞生物学，尤其是其功能可用性（调节剂），并且可能会调节下游CPLX函数，从而以活动依赖性方式（效应子）释放发射机。