The CNK2 scaffold interacts with vilse and modulates Rac cycling during spine morphogenesis in hippocampal neurons.
The CNK2 scaffold interacts with vilse and modulates Rac cycling during spine morphogenesis in hippocampal neurons.
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DOI：
10.1016/j.cub.2014.02.036
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发表时间：
2014-03-31
期刊：
影响因子：
9.2
通讯作者：
Morrison, Deborah K.
中科院分区：
文献类型：
--
作者：
Lim, Junghwa;Ritt, Daniel A.;Zhou, Ming;Morrison, Deborah K.
蛋白质支架在信号转导中起着重要作用，其功能是促进蛋白质相互作用并将关键途径组分定位于特定的信号位点。KSR-2（CNK 2）的连接增强子是一种神经元表达的支架，最近与非综合征性X连锁精神发育迟滞（MRX）有关。MRX患者有认知功能缺陷，其神经元经常表现出树突棘异常，表明CNK 2在突触信号传导和/或棘形成中的作用。为了深入了解CNK 2如何促进这些过程，我们使用质谱法来鉴定与内源性CNK 2支架相互作用的蛋白质。在这里，我们报告CNK 2的主要结合伴侣是Vilse/ARHGAP 39，CNK 2复合物富含参与Rac/Cdc 42信号传导的蛋白质，包括Rac 1本身，α-/β-PIX，GIT 1/2，PAK 3/4和细胞粘连素家族成员。CNK 2和Vilse之间的结合被认为是组成性的，由Vilse的WW-domain和CNK 2中的脯氨酸基序介导。通过突变体分析，蛋白质消耗和救援实验，我们确定CNK 2作为一个空间调制器的Rac循环在脊柱形态发生，并发现与Vilse的相互作用是至关重要的保持RacGDP/GTP水平在脊柱形成所需的平衡。
Protein scaffolds play an important role in signal transduction, functioning to facilitate protein interactions and localize key pathway components to specific signaling sites. Connector enhancer of KSR-2 (CNK2) is a neuronally-expressed scaffold recently implicated in non-syndromic, X-linked mental retardation (MRX). MRX patients have deficits in cognitive function and their neurons often exhibit dendritic spine abnormalities, suggesting a role for CNK2 in synaptic signaling and/or spine formation. To gain insight regarding how CNK2 might contribute to these processes, we used mass spectrometry to identify proteins that interact with the endogenous CNK2 scaffold. Here, we report that the major binding partner of CNK2 is Vilse/ARHGAP39 and that CNK2 complexes are enriched for proteins involved in Rac/Cdc42 signaling, including Rac1 itself, α-/β-PIX, GIT1/2, PAK3/4, and members of the cytohesin family. Binding between CNK2 and Vilse was found to be constitutive, mediated by the WW-domains of Vilse and a proline motif in CNK2. Through mutant analysis, protein depletion and rescue experiments, we identify CNK2 as a spatial modulator of Rac cycling during spine morphogenesis and find that the interaction with Vilse is critical for maintaining RacGDP/GTP levels at a balance required for spine formation.
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影响因子：
9.2
作者：
Bumeister, R;Rosse, C;White, MA
通讯作者：
White, MA
DOI：
10.1073/pnas.0409325102
发表时间：
2005-03-22
影响因子：
11.1
作者：
Hu, HL;Li, M;Bashaw, GJ
通讯作者：
Bashaw, GJ
影响因子：
10.5
作者：
Lundström, A;Gallio, M;Samakovlis, C
通讯作者：
Samakovlis, C
影响因子：
1.1
作者：
Houge, G.;Rasmussen, I. H.;Hovland, R.
通讯作者：
Hovland, R.
DOI：
10.1006/bbrc.2000.2475
发表时间：
2000-04-13
影响因子：
3.1
作者：
Yao, I;Ohtsuka, T;Hata, Y
通讯作者：
Hata, Y