The LRRK2-related Roco kinase Roco2 is regulated by Rab1A and controls the actin cytoskeleton
The LRRK2-related Roco kinase Roco2 is regulated by Rab1A and controls the actin cytoskeleton
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DOI：
10.1091/mbc.e10-12-0937
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发表时间：
2011-07-01
影响因子：
3.3
通讯作者：
Firtel, Richard A.
中科院分区：
文献类型：
--
作者：
Kicka, Sebastian;Shen, Zhouxin;Firtel, Richard A.
我们确定了正确伪足形成所需的新途径。我们发现 Roco2 是一种富含亮氨酸重复激酶 2 (LRRK2) 相关的 Roco 激酶，它会响应趋化剂刺激而被激活，并通过在需要 Rab1A 的途径中调节皮质 F-肌动蛋白聚合和伪足延伸来帮助介导细胞极化和趋化性。我们发现 Roco2 在体内结合小 GTPase Rab1A 以及 F-肌动蛋白交联蛋白 filamin（肌动蛋白结合蛋白 120，abp120）。我们表明，活性 Rab1A (Rab1A-GTP) 是体内 Roco2 激酶活性所必需的，并可调节 Roco2 激酶活性，而细丝蛋白位于 Roco2 下游，在趋化性和随机细胞运动过程中控制伪足延伸。因此，我们的研究发现了一条新的信号通路，涉及 Rab1A 并控制肌动蛋白细胞骨架和伪足延伸，从而控制细胞极性和运动性。这些发现还可能对后生动物中其他 Roco 激酶（可能包括 LRRK2）的调节产生影响。
We identify a new pathway that is required for proper pseudopod formation. We show that Roco2, a leucine-rich repeat kinase 2 (LRRK2)-related Roco kinase, is activated in response to chemoattractant stimulation and helps mediate cell polarization and chemotaxis by regulating cortical F-actin polymerization and pseudopod extension in a pathway that requires Rab1A. We found that Roco2 binds the small GTPase Rab1A as well as the F-actin cross-linking protein filamin (actin-binding protein 120, abp120) in vivo. We show that active Rab1A (Rab1A-GTP) is required for and regulates Roco2 kinase activity in vivo and that filamin lies downstream from Roco2 and controls pseudopod extension during chemotaxis and random cell motility. Therefore our study uncovered a new signaling pathway that involves Rab1A and controls the actin cytoskeleton and pseudopod extension, and thereby, cell polarity and motility. These findings also may have implications in the regulation of other Roco kinases, including possibly LRRK2, in metazoans.