Research and collaboration

Our group has used structural biology, biochemistry and cell biology. Recently we have shown that:

  • many parts of Filamin interact with other proteins so that the other protein forms an additional beta-strand next the strand C of Filamin immunoglobulin-like domains (Nakamura et al., 2006; Kiema et al. 2006; Takala et al., 2008; Lad at al., 2008; Nakamura et al., 2009), 
  • in some parts of Filamin this interaction site is masked by the neighboring domains (Lad et al., 2007; Heikkinen et al., 2009),
  • this masking interaction is regulated by mechanical pulling forces (Pentikäinen and Ylänne, 2009; Rognoni et al., 2012), and
  • mechanical properties of filamins are important for tissue development (Huelsmann et al., 2013, Huelsmann et al., 2016)
  • filamin mutations alter Drosophila flight muscle attachment sites and Z lines (Green et al., 2018)
  • talin-vinculin-filamin-WASH are part of a mechanosensitive regulatory network in muscle (Green et al., 2018)

Future Goals: 

Our major goal is to understand how the interactions of Filamins can be regulated and how these interactions contribute to cell regulation.

One of our working hypotheses is that Filamin can act as a mechanosensor so that mechanical stretch generated by actin cytoskeleton in response to extracellular clues exposes the masked binding sites on Filamin. Alternatively, multiple interactions of Filamin may regulate each others. We are particularly interested to a region close to the C-terminus of Filamin which seems to be a hot stop for interactions. We are studying the structure and properties of this region.

Currently, we are using x-ray crystallography, protein NMR, biochemical interaction experiments, live cell microscopy and model organism Drosophila melanogaster in our studies.