The activities of the C-terminal regions of the formin protein Disheveled-associated activator of morphogenesis (DAAM) in actin dynamics

Andrea Teréz Vig, István Földi, Szilárd Szikora, Ede Migh, Rita Gombos, Mónika Ágnes Tóth, Tamás Huber, Réka Pintér, G. Talián, József Mihály, B. Bugyi

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Disheveled-associated activator of morphogenesis (DAAM) is a diaphanous-related formin protein essential for the regulation of actin cytoskeleton dynamics in diverse biological processes. The conserved formin homology 1 and 2 (FH1–FH2) domains of DAAM catalyze actin nucleation and processively mediate filament elongation. These activities are indirectly regulated by the N- and C-terminal regions flanking the FH1–FH2 domains. Recently, the C-terminal diaphanous-autoregulatory domain (DAD) and the C terminus (CT) of formins have also been shown to regulate actin assembly by directly interacting with actin. Here, to better understand the biological activities of DAAM, we studied the role of DAD-CT regions of Drosophila DAAM in its interaction with actin with in vitro biochemical and in vivo genetic approaches. We found that the DAD-CT region binds actin in vitro and that its main actin-binding element is the CT region, which does not influence actin dynamics on its own. However, we also found that it can tune the nucleating activity and the filament end–interaction properties of DAAM in an FH2 domain-dependent manner. We also demonstrate that DAD-CT makes the FH2 domain more efficient in antagonizing with capping protein. Consistently, in vivo data suggested that the CT region contributes to DAAM-mediated filopodia formation and dynamics in primary neurons. In conclusion, our results demonstrate that the CT region of DAAM plays an important role in actin assembly regulation in a biological context.

Original languageEnglish
Pages (from-to)13566-13583
Number of pages18
JournalJournal of Biological Chemistry
Issue number33
Publication statusPublished - Jan 1 2017


ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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