MOCA induces membrane spreading by activating Rac1
MOCA induces membrane spreading by activating Rac1
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DOI：
10.1074/jbc.m311275200
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发表时间：
2004-04-02
影响因子：
4.8
通讯作者：
Kimura, H
中科院分区：
文献类型：
--
作者：
Namekata, K;Enokido, Y;Kimura, H
细胞粘附蛋白（莫卡）的修饰物，或Dock 3，最初被鉴定为早老素结合蛋白（PBP），属于Dock 180蛋白家族，特异性定位于神经元。在这里，我们证明，莫卡结合Rac 1，并增强其活性，这导致c-Jun氨基末端激酶（JNK）的激活，并导致细胞形态的变化。法尼基化的莫卡，这是本地化的质膜，增强Rac 1和JNK的激活比野生型莫卡更显着，和细胞表达法尼基化的莫卡显示扁平的形态类似于那些表达的组成型活性突变体的Rac 1，Rac 1 Q61 L。在聚-D-赖氨酸包被的培养皿上，内源性莫卡集中在宽膜突起（板状伪足）的前缘，其中肌动蛋白丝共定位。在皮层神经元的原代培养物中，莫卡也与肌动蛋白一起集中在生长锥上。这些观察结果表明，莫卡可能通过调节Rac 1的活性诱导细胞骨架重组和细胞粘附的变化。
The modifier of cell adhesion protein ( MOCA), or Dock3, initially identified as presenilin-binding protein (PBP), belongs to the Dock180 family of proteins and is localized specifically in neurons. Here we demonstrate that MOCA binds to Rac1 and enhances its activity, which leads to the activation of c-Jun NH2-terminal kinase (JNK) and causes changes in cell morphology. Farnesylated MOCA, which is localized in the plasma membrane, enhances the activation of Rac1 and JNK more markedly than wild-type MOCA, and cells expressing farnesylated MOCA show flattened morphology similar to those expressing a constitutive active mutant of Rac1, Rac1Q61L. On poly-D-lysine-coated dishes, endogenous MOCA is concentrated on the leading edge of broad membrane protrusions (lamellipodia) where actin filaments are co-localized. MOCA is also concentrated with actin on the growth cone in primary cultures of cortical neurons. These observations suggest that MOCA may induce cytoskeletal reorganization and changes in cell adhesion by regulating the activity of Rac1.