Analyzing the Complexins of the photoreceptor ribbon synapses in mouse retina

复合蛋白（Complexins，Cplxs）1和2是高亲和力的SNARE相互作用蛋白。它们调节突触囊泡与质膜融合反应的后期步骤，最有可能是通过稳定SNARE复合物以维持突触囊泡处于释放能力状态。与Cplx 1和2不同的是Cplx 3和4。它们显示出与Cplxs 1和2有限的同源性，具有用于膜相互作用的C末端CAAX盒基序，并且主要在脊椎动物视网膜的带状突触处表达。从以前的研究检查Cplx 3/4双敲除小鼠，我们知道，Cplxs 3和4有不同的功能，从光感受器带状突触的神经递质释放：他们抑制紧张和促进诱发释放，他们发挥了假定的作用，在适应依赖性调节的可用性ribbon-tethered可释放的突触囊泡。然而，迄今为止，该领域中最基本的问题尚未解决：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，这可能取决于它们独特的C末端的法尼基化。此外，我们将寻找相互作用的伙伴，这可能会影响细胞生物学的Cplx 3和4一般和他们的功能可用性，特别是（监管机构），并可能调节下游Cplx功能，从而发射器释放的活性依赖性的方式（效应）。

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).