MODULATION OF GELSOLIN FUNCTION BY PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE
MODULATION OF GELSOLIN FUNCTION BY PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE
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DOI：
10.1038/325362a0
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发表时间：
1987-01-22
期刊：
影响因子：
64.8
通讯作者：
STOSSEL, TP
中科院分区：
文献类型：
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作者：
JANMEY, PA;STOSSEL, TP
肌动蛋白结合蛋白凝溶胶蛋白需要微摩尔浓度的钙离子来切断肌动蛋白丝，以增强其与丝末端的结合，并促进单体肌动蛋白聚合成凝胶1 -5。由于细胞内[Ca 2 +]6- 8和肌动蛋白聚合8，9的瞬时增加伴随着细胞对某些刺激的反应，因此有人认为凝溶胶蛋白调节伴随着这种细胞激活的肌动蛋白丝的可逆组装。但其他证据10 - 12表明，这些活性不需要增加细胞质[Ca 2 +]，并且一旦在体外存在Ca 2+的情况下形成肌动蛋白-凝溶胶蛋白复合物，去除游离Ca 2+仅导致两个结合的肌动蛋白单体中的一个从凝溶胶蛋白解离，并且所得二元复合物不能切断肌动蛋白单体4，13-15。细胞凝溶胶蛋白-肌动蛋白复合物可以解离的发现16表明凝溶胶蛋白也发生了不依赖于Ca 2+的调节。在这里，我们表明，像profilin-actin complex的解离17，磷脂酰肌醇4，5-二磷酸，在细胞刺激18，19期间经历快速周转，强烈抑制凝溶胶蛋白的肌动蛋白切割特性，抑制这种蛋白质的成核能力不太强烈，并恢复凝溶胶蛋白-肌动蛋白复合物的切割活性的潜力。
The actin-binding protein gelsolin requires micromolar concentrations of calcium ions to sever actin filaments, to potentiate its binding to the end of the filament and to promote the polymerization of monomeric actin into filaments1–5. Because transient increases in both intracellular [Ca2+]6–8and actin polymerization8,9accompany the cellular response to certain stimuli, it has been suggested that gelsolin regulates the reversible assembly of actin filaments that accompanies such cellular activations. But other evidence10–12suggests that these activities do not need increased cytoplasmic [Ca2+] and that once actin–gelsolin complexes form in the presence of Ca2+in vitro, removal of free Ca2+causes dissociation of only one of two bound actin monomers from gelsolin and the resultant binary complexes cannot sever actin filaments4,13–15. The finding that cellular gelsolin–actin complexes can be dissociated16suggests that a Ca2+-independent regulation of gelsolin also occurs. Here we show that, like the dissociation of profilin–actin complexes17, phosphatidylinositol 4,5-bisphosphate, which undergoes rapid turnover during cell stimulation18,19, strongly inhibits the actin filament-severing properties of gelsolin, inhibits less strongly the nucleating ability of this protein and restores the potential for filament-severing activity to gelsolin–actin complexes.