Direct stimulation of receptor-controlled phospholipase D1 by phospho-cofilin
Direct stimulation of receptor-controlled phospholipase D1 by phospho-cofilin
复制标题
DOI：
10.1038/sj.emboj.7601852
复制
发表时间：
2007-10-03
期刊：
影响因子：
11.4
通讯作者：
Schmidt, Martina
中科院分区：
文献类型：
--
作者：
Han, Li;Stope, Matthias B.;Schmidt, Martina
控制肌动蛋白动力学的cofilin的活性状态由磷酸化-去磷酸化循环驱动。lim激酶磷酸化cofilin导致其失活，这一过程由14-3-3 zeta支持，并由弹弓磷酸酶去磷酸化逆转。在这里，我们报告了一个新的细胞功能的磷酸化-去磷酸化循环的cofilin。我们证明了毒蕈碱受体介导的磷脂酶D1 （PLD1）的刺激是由lim激酶、弹弓磷酸酶和14-3-3 zeta控制的，并且需要可磷酸化的cofilin。Cofilin直接和特异性地与PLD1相互作用，在被LIM-kinase1磷酸化后，刺激PLD1活性，这种作用被磷酸化模拟Cofilin突变体模仿。cofilin与PLD1的相互作用受受体控制，包含PLD1特异性片段（aa 585 -712）。该片段的表达抑制受体诱导的cofilin-PLD1相互作用以及PLD刺激和肌动蛋白应激纤维的形成。这些数据表明，迄今为止被认定为失活的phospho-cofilin具有活跃的细胞功能，并提示phospho-cofilin通过其对PLD1的刺激作用可能控制多种细胞功能。
The activity state of cofilin, which controls actin dynamics, is driven by a phosphorylation -dephosphorylation cycle. Phosphorylation of cofilin by LIM-kinases results in its inactivation, a process supported by 14-3-3 zeta and reversed by dephosphorylation by slingshot phosphatases. Here we report on a novel cellular function for the phosphorylation -dephosphorylation cycle of cofilin. We demonstrate that muscarinic receptor-mediated stimulation of phospholipase D1 (PLD1) is controlled by LIM-kinase, slingshot phosphatase as well as 14-3-3 zeta, and requires phosphorylatable cofilin. Cofilin directly and specifically interacts with PLD1 and upon phosphorylation by LIM-kinase1, stimulates PLD1 activity, an effect mimicked by phosphorylation-mimic cofilin mutants. The interaction of cofilin with PLD1 is under receptor control and encompasses a PLD1-specific fragment (aa 585 -712). Expression of this fragment suppresses receptor-induced cofilin-PLD1 interaction as well as PLD stimulation and actin stress fiber formation. These data indicate that till now designated inactive phospho-cofilin exhibits an active cellular function, and suggest that phospho-cofilin by its stimulatory effect on PLD1 may control a large variety of cellular functions.