Neuron-Subtype-Specific Expression, Interaction Affinities, and Specificity Determinants of DIP/Dpr Cell Recognition Proteins.

Neuron-Subtype-Specific Expression, Interaction Affinities, and Specificity Determinants of DIP/Dpr Cell Recognition Proteins.
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DIP/Dpr 细胞识别蛋白的神经元亚型特异性表达、相互作用亲和力和特异性决定因素。

DOI:
10.1016/j.neuron.2018.10.046
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发表时间:
2018-12-19
期刊:
影响因子:
16.2
通讯作者:
Shapiro L
Shapiro L
中科院分区:
医学1区
文献类型:
--
作者:
Cosmanescu F;Katsamba PS;Sergeeva AP;Ahlsen G;Patel SD;Brewer JJ;Tan L;Xu S;Xiao Q;Nagarkar-Jaiswal S;Nern A;Bellen HJ;Zipursky SL;Honig B;Shapiro L

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DIP和Dpr神经元识别蛋白之间的结合已经被提出来调节果蝇视觉系统中板层和髓质神经元之间的突触连接。每个板层神经元先前被证明表达许多DALF。在这里,我们证明,相比之下,他们的突触的合作伙伴通常表达一个或两个DIP,与板层神经元表达的DIPs相匹配的结合特异性。深入了解DIP/DPR相互作用的分子逻辑需要对这些蛋白质的性质进行定量研究。因此,我们产生了一个定量的基于亲和力的DIP/Dpr相互作用组的所有DIP/Dpr蛋白家族成员。这揭示了广泛的亲和力,并确定了一些DIP和一些DIPs的嗜同性结合。这些数据,沿着全长胞外域DIP/Dpr和DIP/DIP晶体结构,导致DIP/Dpr特异性的分子决定因素的鉴定。这种结构知识,沿着一套全面的定量结合亲和力,为体内功能研究提供了新的工具。DIP/Dpr相互作用有助于果蝇神经系统的模式。Cosmanescu等人量化了它们的相互作用并绘制了髓质神经元中DIP的表达。结构研究确定了DIP/Dpr相互作用的特异性决定因素,并揭示了DIP/DIP同二聚体的保守结构。
Binding between DIP and Dpr neuronal-recognition proteins has been proposed to regulate synaptic connections between lamina and medulla neurons in the Drosophila visual system. Each lamina neuron was previously shown to express many Dprs. Here, we demonstrate, by contrast, that their synaptic partners typically express one or two DIPs, with binding specificities matched to the lamina neuron-expressed Dprs. A deeper understanding of the molecular logic of DIP/Dpr interaction requires quantitative studies on the properties of these proteins. We thus generated a quantitative affinity-based DIP/Dpr interactome for all DIP/Dpr protein family members. This revealed a broad range of affinities and identified homophilic binding for some DIPs and some Dprs. These data, along with full-length ectodomain DIP/Dpr and DIP/DIP crystal structures, led to the identification of molecular determinants of DIP/Dpr specificity. This structural knowledge, along with a comprehensive set of quantitative binding affinities, provides new tools for functional studies in vivo. DIP/Dpr interactions help to pattern the Drosophila nervous system. Cosmanescu et al. quantify their interactions and map DIP expression in medulla neurons. Structural studies identify specificity determinants of DIP/Dpr interactions and reveal a conserved architecture for DIP/DIP homodimers.
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