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Functions of cofilin, an actin-regulating protein

肌动蛋白丝切蛋白（一种肌动蛋白调节蛋白）的功能

基本信息

批准号：
09101002
负责人：
IIDA Kazuko
金额：
$ 131.84万
依托单位：
The Tokyo Metropolitan Institute of Medical Science
依托单位国家：
日本
项目类别：
Grant-in-Aid for Specially Promoted Research
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 2000
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09101002/
关键词：
actin cofilin cell movement actrin filament severing acceleration of actin filament depolymerization growth cone collapse Aip1 cellular slime mold Cap1 収縮高浸透圧・ストレス神経突起 AIP1 高浸透圧ストレス GFP アクチン調節蛋白質 AIP 1

项目摘要

1) We improved the conventional method using fluorescently labeled actin, then demonstrated that cofilin severs actin filaments and accelerates monomer release at their pointed ends. Under substoichiometric conditions, 0.8 μM cofilin cut filamentous actin (2.2 μM) about every 270 monomer subunits and increased the depolymerization rate 5.7-fold at pH 7.1.2) Using cultured mammalian cell and Xnopus oocyte cell extracts, we identified two proteins, which bound to actin/cofilin comuln, to be Aipl and CAP.Yeast Aip1 was also found as a factor which suppresses the ts-phenotype of cof1 mutation. In Physarum polycepharum, a heat stress-induced cist-specific actin-binding protein was identified as Aip1. Aip1 suguments both actin filaments-severing and depolymerization-accelerating activities of cofilin.3) we identified a novel type of cofilin family member, cofilin-2, in D.discoideum. Cofilin- 2 consists of 143 amino acid residues. Cofilin-2 shows a significant homology (30.6% identity) to cof … More ilin-1 in its entire sequence, but does not retain some residues conserved among the cofilin family memners, suggesting that cofilin-2 belongs to a novel type of cofilin family. Purified cofilin-2 depolymerized actin filaments in a dose- and pH-dependent manner, but did not cosediment with actin filaments while cofilin-1 did. Cofilin-2 was not expressed in vegetative cells, and expresseion of coffin-2 is reduced during aggregation stage of development.4) we investigated the role of LIM-kinase 1, a protein that phosphorylates an actin depolymerizing protein, cofilin, in semaphorin 3A-induced growth cone collapse. We found that semaphorin 3A induces phosphorylation and dephosphorylation of cofilin at growth cones sequentially. A synthetic cell-permeable peptide containing a cofilin phosphorylation site inhibited LIM-kinase in vitro and in vivo, and essentially suppressed semaphorin 3A-induced growth cone collaplse. These data suggest that phosphorylation of cofilin by LIM-kinase is a critical signaling event in growht cone collapse by semaphorin 3A. Less

1)我们使用荧光标记的肌动蛋白改进了传统的方法，然后证明了cofilin切断肌动蛋白丝并加速其尖端的单体释放。在亚化学计量条件下，0.8 μM cofilin切割丝状肌动蛋白，（2.2 μM），并且在pH 7.1下使解聚速率增加5.7倍。2）使用培养的哺乳动物细胞和Xnopus卵母细胞提取物，我们鉴定了两种蛋白质，其结合肌动蛋白/cofilin comuln，酵母Aip 1也被发现是抑制cof 1突变的ts-表型的因子。在多头绒泡菌（Physarum polycepharum）中，热应激诱导的cist特异性肌动蛋白结合蛋白被鉴定为Aip 1。Aip 1表明cofilin同时具有肌动蛋白切割和解聚加速的活性。3）我们在盘状杜父藻中鉴定了一种新型的cofilin家族成员cofilin-2。Cofilin- 2由143个氨基酸残基组成。Cofilin-2与COF有30.6%的同源性 ...更多信息 Cofilin-1在其整个序列中，但不保留cofilin家族成员中保守的一些残基，表明cofilin-2属于一种新类型的cofilin家族。纯化的cofilin-2解聚肌动蛋白丝的剂量和pH值依赖性的方式，但没有共沉淀与肌动蛋白丝，而cofilin-1。Cofilin-2在营养细胞中不表达，而coffin-2在发育的聚集阶段表达减少。4）我们研究了LIM-kinase 1（一种磷酸化肌动蛋白解聚蛋白Cofilin的蛋白质）在脑信号蛋白3A诱导的生长锥塌陷中的作用。我们发现，semaphorin 3A诱导cofilin在生长锥的磷酸化和去磷酸化顺序。一种合成的细胞渗透性肽含有一个cofilin磷酸化位点抑制LIM-kinase在体外和体内，并基本上抑制semaphorin 3A诱导的生长锥collaplse。这些数据表明，由LIM-kinase磷酸化的cofilin是一个关键的信号转导事件，在生长锥崩溃的semaphorin 3A。少