Novel activators of Arp2/3 complex, JMY and WHDC1

Arp 2/3复合物是一种重要的肌动蛋白成核剂，在多种细胞过程中发挥作用。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（NPF），根据Arp 2/3复合物激活的机制，这些蛋白质被细分为I类和II类NPF。哺乳动物细胞表达五种被称为WASP/WAVE家族的特征性和突出的I类NPF，其控制肌动蛋白成核以实现不同的细胞功能，例如内吞作用和片状脂质体突出。I类NPF的特征在于保守的C-末端VCA模块，其是激活Arp 2/3复合物所必需的且足够的。在哺乳动物基因组中检测到可能构成I类NPF的另外三个基因，即最近描述的WASH以及新因子JMY（连接介导和调节蛋白）和WHDC 1（WASP同源2结构域包含1）。尽管对WASP/WAVE蛋白进行了深入的研究，但由于Arp 2/3依赖过程的许多开放性问题，我们决定研究这两种新蛋白。我们将首先集中我们的特点无处不在的JMY。其C-末端结构域特征包含类似于N-WASP 2的高度保守的V-模块，而没有观察到与V和酸性A-区之间的C-伸展的同源性（VV-A）。此外，JMY包括一个中央卷曲螺旋形成区，显示模糊的相似性，单拷贝基因Shootin 1，这是牵连在神经元极性。

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.