Novel mechanisms in actin polymerization: trans-regulation of the Spir-family proteins and Cappuccino-family formins

肌动蛋白聚合的新机制：Spir家族蛋白和Cappuccino家族福明斯的反式调节

• 批准号: 5407672
• 负责人: Professor Dr. Eugen Kerkhoff
• 金额: --
• 依托单位: Labor Molekulare Zellbiology (Kerkhoff Lab)
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2003
• 资助国家: 德国
• 起止时间: 2002-12-31 至 2009-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/5407672?language=en
• 关键词: Novel; mechanisms; actin; polymerization; trans

The Drosophila spire and cappuccino mutants were identified in same genetic screen and have a nearly identical phenotype. The genes are required for the polarization of the Drosophila oocyte. The Spir and Cappuccino proteins belong to two distinct classes of actin organizers. The N-terminal region of the Spir protein shows sequence similarities to the Wiskott-Aldrich Syndrome protein (WASP), in that it encodes a cluster of four WH2 domains and an acidic region. The Cappuccino protein belongs to the formin protein family. Recently it has been shown that the yeast formin bni1p induces the formation of actin cables. Spir proteins colocalize with the Rab11 GTPase at the trans-Golgi network and post-Golgi vesicles and have a function in vesicle transport processes. The specific subcellular localization of the Spir proteins is mediated by a C-terminal FYCW zinc finger motif. In yet unpublished studies we have shown that both, Spir and Cappuccino, are localized at vesicle actin comet tails. This indicates a function of the proteins in actin dependent propulsion of cytoplasmic vesicles. In addition, we found both proteins highly phosphorylated in response to the activation of the p38 MAP kinase, which points to a common regulatory mechanism by MAP kinase signaling. Here we describe experiments to analyze the regulation and potential cooperation of the two actin organizers in the formation of vesicle actin comet tails.

果蝇的尖顶和卡布奇诺突变体在相同的基因筛选中被鉴定出来，并且具有几乎相同的表型。这些基因是果蝇卵母细胞极化所必需的。Spir蛋白和Cappuccino蛋白属于两种不同的肌动蛋白组织体。Spir蛋白的n端区域与Wiskott-Aldrich综合征蛋白（WASP）的序列相似，编码一个由四个WH2结构域组成的簇和一个酸性区域。卡布奇诺蛋白属于双胍蛋白家族。最近有研究表明，酵母双胍bni1p可诱导肌动蛋白索的形成。Spir蛋白与Rab11 GTPase在反式高尔基网络和后高尔基囊泡中共定位，并在囊泡运输过程中发挥作用。Spir蛋白的特异亚细胞定位是由c端FYCW锌指基序介导的。在尚未发表的研究中，我们已经表明，Spir和Cappuccino都定位于囊泡肌动蛋白彗尾。这表明蛋白质在肌动蛋白依赖的细胞质囊泡推进中的功能。此外，我们发现这两种蛋白在响应p38 MAP激酶的激活时高度磷酸化，这表明MAP激酶信号的共同调节机制。在这里，我们描述了实验来分析两个肌动蛋白组织者在囊泡肌动蛋白彗星尾巴形成中的调节和潜在的合作。