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 SNARE 相互作用蛋白。它们调节突触小泡与质膜融合反应的后期步骤，很可能是通过稳定 SNARE 复合体来维持突触小泡处于释放能力状态。与 Cplxs 1 和 2 不同的是 Cplxs 3 和 4。它们与 Cplxs 1 和 2 表现出有限的同源性，具有用于膜相互作用的 C 端 CAAX-box 基序，并且主要在脊椎动物视网膜的带状突触处表达。从之前对 Cplx 3/4 双敲除小鼠的研究中，我们知道 Cplx 3 和 4 在光感受器带突触释放神经递质方面具有不同的功能：它们抑制强直并促进诱发释放，并且它们在适应中发挥假定的作用丝带系留的可释放突触小泡的可用性的依赖性调节。然而，迄今为止，该领域最基本的问题尚未得到解决：视网膜 Cplx 功能的潜在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 的适应依赖性表达（RNA、蛋白质），以及它们在可溶性和不溶性（膜相关）形式之间的转换，这可能取决于其独特 C 末端的法呢基化。此外，我们将寻找相互作用伙伴，这可能会影响Cplxs 3和4的细胞生物学，特别是它们的功能可用性（调节器），并且可能会调节下游Cplx功能，从而以活性依赖的方式释放递质（效应器）。