Different roles of the small GTPases Rac1, Cdc42, and RhoG in CALEB/NGC‐induced dendritic tree complexity
Different roles of the small GTPases Rac1, Cdc42, and RhoG in CALEB/NGC‐induced dendritic tree complexity
复制标题
小 GTPases Rac1、Cdc42 和 RhoG 在 CALEB/NGC 诱导的树突树复杂性中的不同作用
DOI：
10.1111/jnc.13735
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发表时间：
2016
影响因子：
4.7
通讯作者：
Schumacher S
中科院分区：
文献类型：
--
作者：
Schulz J;Franke K;Frick M;Schumacher S
Rho GTP酶在细胞骨架重组的调节中起重要作用。关于Rho GTP酶在导致细胞骨架重排的不同信号通路中的个体功能，已经阐述了许多方面。然而，主要的问题还有待回答的整合和不同的Rho GTP酶在调节细胞骨架的基本生理事件，如神经元过程分化的信号层次。在这里，我们调查的作用，小GTP酶Rac 1，Cdc 42，和RhoG在定义树突状树的复杂性刺激的跨膜表皮生长因子家族成员CALEB/NGC。结合原代海马神经元的功能获得和功能丧失分析，我们发现Rac 1对CALEB/NGC介导的树突分支至关重要。cdc 42降低了树突树的复杂性。有趣的是，我们确定棕榈酰化的Cdc 42亚型对树突状生长和树突状分支产生不利影响，而异戊烯化的Cdc 42亚型则不会。与Rac 1相反，CALEB/NGC和Cdc 42在调节树突状树复杂性方面并不直接互连。与Rac 1不同，Rac 1相关的GTdR RhoG通过作用于CALEB/NGC的上游来降低树突树的复杂性。从机制上讲，CALEB/NGC激活Rac 1，RhoG减少了位于细胞膜上Rac 1激活正确位点的CALEB/NGC的量。因此，Rac 1、Cdc 42和RhoG在调节CALEB/NGC诱导的树突树复杂性的不同层次上发挥着非常特异和非冗余的功能。Rho GTP酶在树突分支中发挥着重要作用。CALEB/NGC是表皮生长因子（EGF）家族的跨膜成员，其介导依赖于Rac 1的树突状分支。CALEB/NGC刺激Rac 1活性。RhoG通过减少质膜上CALEB/NGC的量来抑制CALEB/NGC介导的树突状分支。棕榈酰化的，但不是异戊二烯化形式的GTdR Cdc 42减少树突状分支。CALEB/NGC和Cdc 42在调节树突状分支中不直接互连。因此，CALEB/NGC在质膜上组织Rho GT3信号传导模块以形成树突状树。
Rho GTPases play prominent roles in the regulation of cytoskeletal reorganization. Many aspects have been elaborated concerning the individual functions of Rho GTPases in distinct signaling pathways leading to cytoskeletal rearrangements. However, major questions have yet to be answered regarding the integration and the signaling hierarchy of different Rho GTPases in regulating the cytoskeleton in fundamental physiological events like neuronal process differentiation. Here, we investigate the roles of the small GTPases Rac1, Cdc42, and RhoG in defining dendritic tree complexity stimulated by the transmembrane epidermal growth factor family member CALEB/NGC. Combining gain‐of‐function and loss‐of‐function analysis in primary hippocampal neurons, we find that Rac1 is essential for CALEB/NGC‐mediated dendritic branching. Cdc42 reduces the complexity of dendritic trees. Interestingly, we identify the palmitoylated isoform of Cdc42 to adversely affect dendritic outgrowth and dendritic branching, whereas the prenylated Cdc42 isoform does not. In contrast to Rac1, CALEB/NGC and Cdc42 are not directly interconnected in regulating dendritic tree complexity. Unlike Rac1, the Rac1‐related GTPase RhoG reduces the complexity of dendritic trees by acting upstream of CALEB/NGC. Mechanistically, CALEB/NGC activates Rac1, and RhoG reduces the amount of CALEB/NGC that is located at the right site for Rac1 activation at the cell membrane. Thus, Rac1, Cdc42, and RhoG perform very specific and non‐redundant functions at different levels of hierarchy in regulating dendritic tree complexity induced by CALEB/NGC.Rho GTPases play a prominent role in dendritic branching. CALEB/NGC is a transmembrane member of the epidermal growth factor (EGF) family that mediates dendritic branching, dependent on Rac1. CALEB/NGC stimulates Rac1 activity. RhoG inhibits CALEB/NGC‐mediated dendritic branching by decreasing the amount of CALEB/NGC at the plasma membrane. Palmitoylated, but not prenylated form of the GTPase Cdc42 decreases dendritic branching. CALEB/NGC and Cdc42 are not directly interconnected in regulating dendritic branching. Thus, CALEB/NGC organizes a Rho GTPase signaling module at the plasma membrane for shaping dendritic trees.
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影响因子：
9.2
作者：
Estrach, S;Schmidt, S;Debant, A
通讯作者：
Debant, A
影响因子：
4.1
作者：
Wirth, Alexander;Chen-Wacker, Chen;Ponimaskin, Evgeni
通讯作者：
Ponimaskin, Evgeni
影响因子：
4.8
作者：
Brandt, Nicola;Franke, Kristin;Schumacher, Stefan
通讯作者：
Schumacher, Stefan
DOI：
10.1073/pnas.0509032102
发表时间：
2005-12-06
影响因子：
11.1
作者：
Chen, JG;Rasin, MR;Sestan, N
通讯作者：
Sestan, N
影响因子：
3.3
作者：
Noritake, J;Fukata, M;Kaibuchi, K
通讯作者：
Kaibuchi, K