Activation of LIMK1 by binding to the BMP receptor, BMPRII, regulates BMP-dependent dendritogenesis
Activation of LIMK1 by binding to the BMP receptor, BMPRII, regulates BMP-dependent dendritogenesis
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DOI：
10.1038/sj.emboj.7600418
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发表时间：
2004-12-08
期刊：
影响因子：
11.4
通讯作者：
Attisano, L
中科院分区：
文献类型：
--
作者：
Lee-Hoeflich, ST;Causing, CG;Attisano, L
树突的生长和形态分化是神经元正常连接和神经功能建立的关键过程。一个外在因素，BMP7，已被证明能特异性地影响树突形态发生；然而，发生这种情况的潜在机制尚不清楚。在这里，我们发现LIM激酶1 （LIMK1）是Rho GTPases的一个关键下游效应物，与BMP受体BMPRII在神经突尖端共定位并与BMPRII结合。这种相互作用是皮层神经元树突树突依赖于bmp诱导所必需的。此外，我们证明了LIMK1与BMPRII的物理相互作用与Rho GTPase Cdc42协同作用，以激活LIMK1的催化活性。因此，这些研究定义了一个不依赖于smad的途径，直接将BMP受体与肌动蛋白动力学的调节联系起来，并提供了细胞外信号如何调节LIMK1活性以允许在树突发生过程中对细胞骨架重塑进行精细空间控制的见解。
The growth and morphological differentiation of dendrites are critical events in the establishment of proper neuronal connectivity and neural function. One extrinsic factor, BMP7, has been shown to specifically affect dendritic morphogenesis; however, the underlying mechanism by which this occurs is unknown. Here we show that LIM kinase 1 (LIMK1), a key downstream effector of Rho GTPases, colocalizes with the BMP receptor, BMPRII, in the tips of neurites and binds to BMPRII. This interaction is required for BMP-dependent induction of the dendritic arbor in cortical neurons. Furthermore, we demonstrate that the physical interaction of LIMK1 with BMPRII synergizes with the Rho GTPase, Cdc42, to activate LIMK1 catalytic activity. These studies thus define a Smad-independent pathway that directly links the BMP receptor to regulation of actin dynamics and provides insights into how extracellular signals modulate LIMK1 activity to permit fine spatial control over cytoskeletal remodelling during dendritogenesis.