Novel activators of Arp2/3 complex, JMY and WHDC1

Arp2/3 复合体、JMY 和 WHDC1 的新型激活剂

• 批准号: 112047629
• 负责人: Professorin Dr. Theresia Stradal
• 金额: --
• 依托单位: Helmholtz-Zentrum für Infektionsforschung (HZI)
• 依托单位国家: 德国
• 项目类别: Research Units
• 财政年份: 2009
• 资助国家: 德国
• 起止时间: 2008-12-31 至 2012-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/112047629?language=en
• 关键词: Novel; activators; Arp2; complex; JMY

Arp2/3 complex is a critical actin nucleator that functions in a variety of cellular processes. It is tightly regulated by a group of proteins with the collective name nucleation promoting factors (NPFs) that are subdivided into class I and class II NPFs, depending on the mechanism of Arp2/3 complex activation. Mammalian cells express five well-characterized and prominent class I NPFs termed WASP/WAVE family, which control actin nucleation for distinct cellular functions such as endocytosis and lamellipodial protrusion. Class I NPFs are characterized by a conserved C-terminal VCA module that is necessary and sufficient to activate Arp2/3 complex. Three more genes that may constitute class I NPFs are detected in the mammalian genome, namely the recently described WASH as well as the novel factors JMY (Junction Mediating and regulatory protein) and WHDC1 (WASP Homology 2 Domain Containing1). Owing to the multitude of open questions on Arp2/3 dependent processes in spite of intense research on WASP/WAVE proteins, we decided to study the two novel proteins. We will initially concentrate our characterization on the ubiquitous JMY. Its C-terminal domain signature contains similar to N-WASP 2 well conserved V-modules, while no homology to the C-stretch between the V and acidic A-region is observed (VV-A). In addition, JMY comprises a central coiled coil forming region, displaying vague similarity to the single copy gene Shootin1, which is implicated in neuronal polarity.

Arp2/3复合物是一种关键的肌动蛋白成核因子，在多种细胞过程中起作用。它受到一组蛋白质的严格调控，这些蛋白质的统称为成核促进因子（nucleation promoting factors, NPFs），根据Arp2/3复合物的激活机制，NPFs又分为I类和II类NPFs。哺乳动物细胞表达被称为WASP/WAVE家族的五种特征明确且突出的I类npf，它们控制肌动蛋白成核以实现不同的细胞功能，如内吞作用和板足突。I类npf的特点是具有一个保守的c端VCA模块，该模块是激活Arp2/3复合物所必需和充分的。在哺乳动物基因组中发现了另外三个可能构成I类npf的基因，即最近描述的WASH以及新因子JMY （Junction mediated and regulatory protein）和WHDC1 （WASP Homology 2 Domain Containing1）。尽管对WASP/WAVE蛋白的研究非常深入，但由于Arp2/3依赖过程仍有许多悬而未决的问题，我们决定研究这两个新蛋白。我们将首先集中描述无处不在的JMY。其c端结构域特征与N-WASP 2具有相似的保守的V-模，而与V区和酸性a区之间的c -延伸没有同源性（VV-A）。此外，JMY包括一个中央卷曲的线圈形成区域，与单拷贝基因Shootin1有模糊的相似性，这与神经元极性有关。

项目成果

Essential role for Abi1 in embryonic survival and WAVE2 complex integrity

• DOI: 10.1073/pnas.1016811108
• 发表时间: 2011-04-26
• 期刊: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• 影响因子: 11.1
• 作者: Dubielecka, Patrycja M.;Ladwein, Kathrin I.;Kotula, Leszek
• 通讯作者: Kotula, Leszek

Microtubules as Platforms for Assaying Actin Polymerization In Vivo

微管作为测定体内肌动蛋白聚合的平台

• DOI: 10.1371/journal.pone.0019931
• 发表时间: 2011
• 期刊: PLoS ONE
• 影响因子: 3.7
• 作者: Oelkers JM;Vinzenz M;Nemethova M;Jacob S;Lai FP;Block J;Szczodrak M;Kerkhoff E;Backert S;Schluter K;Stradal TE;Small JV;Koestler SA;Rottner K
• 通讯作者: Rottner K

High-Resolution X-Ray Structure of the Trimeric Scar/WAVE-Complex Precursor Brk1

• DOI: 10.1371/journal.pone.0021327
• 发表时间: 2011-06-20
• 期刊: PLOS ONE
• 影响因子: 3.7
• 作者: Linkner, Joern;Witte, Gregor;Faix, Jan
• 通讯作者: Faix, Jan

Arp2/3 complex interactions and actin network turnover in lamellipodia

• DOI: 10.1038/emboj.2008.34
• 发表时间: 2008-04-09
• 期刊: EMBO JOURNAL
• 影响因子: 11.4
• 作者: Lai, Frank P. L.;Szczodrak, Malgorzata;Rottner, Klemens
• 通讯作者: Rottner, Klemens