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租约在尖端的末端进行了改善，在数量化的条件下，使用培养的pH 7.1.2时，每270个单体下降速度为0.8μmcofilin切割丝状肌动蛋白（2.2μm）哺乳动物细胞的卵母细胞提取物（结合肌动蛋白/cofilin comrn）与aipl和cap.yeast AIP1一起被发现是抑制COF1突变的TS-表 - 诱导的CIST特异性肌动蛋白结合蛋白所结合蛋白质是抑制TS-phenotype的因素。被识别为AIP1。 COF…在整个序列中更多的ILIN-1，但以剂量和pH值依赖性的方式保留了某些残基Cofilins In-2解聚肌动蛋白丝，而是对肌动蛋白丝的含量并没有cofilin-1在植物细胞中表达，在同意阶段降低了棺材-2的表达，我们研究了lim-激酶1的作用，这种蛋白质是磷酸化肌动蛋白去聚合蛋白Cofilin，在Semaphorin 3A A诱导的生长锥中的作用Semaphorin 3A依次诱导锥形的磷酸化和锥形。 Semaphorin 3a中的cofilin gnaling事件