Mouse profilin 2 regulates endocytosis and competes with SH3 ligand binding to dynamin 1
Mouse profilin 2 regulates endocytosis and competes with SH3 ligand binding to dynamin 1
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DOI：
10.1074/jbc.m503528200
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发表时间：
2006-02-03
影响因子：
4.8
通讯作者：
Witke, W
中科院分区：
文献类型：
--
作者：
Gareus, R;Di Nardo, A;Witke, W
哺乳动物 profilin 是大量表达的肌动蛋白单体结合蛋白，其与 G 肌动蛋白、聚 L-脯氨酸和磷酸肌醇的亲和力高度保守。 Profilins 与大量富含脯氨酸的蛋白质相关；其生理意义和调节知之甚少。在这里，我们发现 profilin 2 通过 dynamin 的 C 端富含脯氨酸的结构域与 dynamin 1 结合，从而与 SH3 配体（如内亲蛋白、两性蛋白和 Grb2）竞争结合，从而干扰内吞机制的组装。我们还提出了大脑特异性小鼠 profilin 2 作为膜运输调节剂的新作用。 profilin 2 的过度表达会抑制内吞作用，而神经元中 profilin 2 的缺乏会导致内吞作用和膜循环的增加。磷脂酰肌醇 4,5-二磷酸从 profilin 2-dynamin 1 复合物以及 profilin 2-肌动蛋白复合物中释放 profilin 2，表明 profilin 2 将磷酸肌醇信号通路分叉至肌动蛋白聚合和内吞作用。
Mammalian profilins are abundantly expressed actin monomerbinding proteins, highly conserved with respect to their affinities for G-actin, poly-L-proline, and phosphoinositides. Profilins associate with a large number of proline-rich proteins; the physiological significance and regulation of which is poorly understood. Here we show that profilin 2 associates with dynamin 1 via the C-terminal proline-rich domain of dynamin and thereby competes with the binding of SH3 ligands such as endophilin, amphiphysin, and Grb2, thus interfering with the assembly of the endocytic machinery. We also present a novel role for the brain-specific mouse profilin 2 as a regulator of membrane trafficking. Overexpression of profilin 2 inhibits endocytosis, whereas lack of profilin 2 in neurons results in an increase in endocytosis and membrane recycling. Phosphatidylinositol 4,5-bisphosphate releases profilin 2 from the profilin 2-dynamin 1 complex as well as from the profilin 2-actin complex, suggesting that profilin 2 is diverging the phosphoinositide signaling pathway to actin polymerization as well as endocytosis.