Novel activators of Arp2/3 complex, JMY and WHDC1

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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.