Leep1 interacts with PIP3 and the Scar/WAVE complex to regulate cell migration and macropinocytosis.
Leep1 interacts with PIP3 and the Scar/WAVE complex to regulate cell migration and macropinocytosis.
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Leep1 与 PIP3 和 Scar/WAVE 复合物相互作用来调节细胞迁移和巨胞饮作用。
DOI：
10.1083/jcb.202010096
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发表时间：
2021-07-05
期刊：
影响因子：
--
通讯作者：
Cai H
中科院分区：
文献类型：
--
作者：
Yang Y;Li D;Chao X;Singh SP;Thomason P;Yan Y;Dong M;Li L;Insall RH;Cai H
Yang等人开发了一种基于蛋白质组学的方法来系统地分离网骨藻中不对称定位的蛋白质，通过该方法他们鉴定了一种名为Leep 1的含LRR结构域的蛋白质。他们的结果表明，PIP 3信号传导、Leep 1和Scar/WAVE复合体的时空协调调节了细胞前缘的突起形态发生。极性对于许多细胞类型中的不同功能至关重要。建立极性需要将特定信号和细胞骨架分子的网络靶向细胞的不同亚区，但极性调节剂的完整补充以及它们的活性如何在空间和时间上整合以形成形态和功能上不同的结构域仍有待发现。在这里，通过使用模型系统Dictyosteoprotein和利用特征性的趋化刺激易位的极性分布的分子，我们开发了一种蛋白质组学筛选方法，通过该方法，我们确定了富含亮氨酸的重复结构域的蛋白质，我们命名为Leep 1作为一种新的极性调节剂。我们结合成像，生物化学和表型分析，以证明Leep 1通过结合PIP 3选择性地定位在细胞的前沿，在那里它通过负调节疤痕/波复合物来调节伪足和巨胞饮杯动力学。PIP 3信号传导、Leep 1和Scar/WAVE复合体的时空协调为在前沿组织扩张结构提供了细胞机制。
Yang et al. develop a proteomics-based approach to systematically isolate asymmetrically localized proteins in Dictyostelium, through which they identify an LRR domain–containing protein named Leep1. Their results reveal that the spatiotemporal coordination of PIP3 signaling, Leep1, and Scar/WAVE complex modulates protrusion morphogenesis at the leading edge of cells. Polarity is essential for diverse functions in many cell types. Establishing polarity requires targeting a network of specific signaling and cytoskeleton molecules to different subregions of the cell, yet the full complement of polarity regulators and how their activities are integrated over space and time to form morphologically and functionally distinct domains remain to be uncovered. Here, by using the model system Dictyostelium and exploiting the characteristic chemoattractant-stimulated translocation of polarly distributed molecules, we developed a proteomic screening approach, through which we identified a leucine-rich repeat domain–containing protein we named Leep1 as a novel polarity regulator. We combined imaging, biochemical, and phenotypic analyses to demonstrate that Leep1 localizes selectively at the leading edge of cells by binding to PIP3, where it modulates pseudopod and macropinocytic cup dynamics by negatively regulating the Scar/WAVE complex. The spatiotemporal coordination of PIP3 signaling, Leep1, and the Scar/WAVE complex provides a cellular mechanism for organizing protrusive structures at the leading edge.
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影响因子：
14.9
作者：
Faix, J;Kreppel, L;Kimmel, AR
通讯作者：
Kimmel, AR
影响因子：
21.3
作者：
Fort L;Batista JM;Thomason PA;Spence HJ;Whitelaw JA;Tweedy L;Greaves J;Martin KJ;Anderson KI;Brown P;Lilla S;Neilson MP;Tafelmeyer P;Zanivan S;Ismail S;Bryant DM;Tomkinson NCO;Chamberlain LH;Mastick GS;Insall RH;Machesky LM
通讯作者：
Machesky LM
影响因子：
8
作者：
Artemenko, Yulia;Lampert, Thomas J.;Devreotes, Peter N.
通讯作者：
Devreotes, Peter N.
DOI：
10.1083/jcb.201001129
发表时间：
2010-07-26
期刊：
The Journal of cell biology
影响因子：
--
作者：
Cai H;Das S;Kamimura Y;Long Y;Parent CA;Devreotes PN
通讯作者：
Devreotes PN
影响因子：
7.7
作者：
Bloomfield G;Traynor D;Sander SP;Veltman DM;Pachebat JA;Kay RR
通讯作者：
Kay RR