Miia Bovellan

Publications (3)26.78 Total impact

• Source

  Available from: Wolfgang Hans

  Article: Missing-in-metastasis MIM/MTSS1 promotes actin assembly at intercellular junctions and is required for integrity of kidney epithelia.

  Juha Saarikangas, Pieta K Mattila, Markku Varjosalo, Miia Bovellan, Janne Hakanen, Julia Calzada-Wack, Monica Tost, Luise Jennen, Birgit Rathkolb, Wolfgang Hans, [......], Eckhard Wolf, Martin Hrabé de Angelis, Mikko J Frilander, Harri Savilahti, Hannu Sariola, Kirsi Sainio, Sanna Lehtonen, Jussi Taipale, Marjo Salminen, Pekka Lappalainen
  [show abstract] [hide abstract]
  ABSTRACT: MIM/MTSS1 is a tissue-specific regulator of plasma membrane dynamics, whose altered expression levels have been linked to cancer metastasis. MIM deforms phosphoinositide-rich membranes through its I-BAR domain and interacts with actin monomers through its WH2 domain. Recent work proposed that MIM also potentiates Sonic hedgehog (Shh)-induced gene expression. Here, we generated MIM mutant mice and found that full-length MIM protein is dispensable for embryonic development. However, MIM-deficient mice displayed a severe urinary concentration defect caused by compromised integrity of kidney epithelia intercellular junctions, which led to bone abnormalities and end-stage renal failure. In cultured kidney epithelial (MDCK) cells, MIM displayed dynamic localization to adherens junctions, where it promoted Arp2/3-mediated actin filament assembly. This activity was dependent on the ability of MIM to interact with both membranes and actin monomers. Furthermore, results from the mouse model and cell culture experiments suggest that full-length MIM is not crucial for Shh signaling, at least during embryogenesis. Collectively, these data demonstrate that MIM modulates interplay between the actin cytoskeleton and plasma membrane to promote the maintenance of intercellular contacts in kidney epithelia.
  Journal of Cell Science 03/2011; 124(Pt 8):1245-55. · 6.11 Impact Factor
• Source

  Available from: Benjamin A Smith

  Article: GMF is a cofilin homolog that binds Arp2/3 complex to stimulate filament debranching and inhibit actin nucleation.

  Meghal Gandhi, Benjamin A Smith, Miia Bovellan, Ville Paavilainen, Karen Daugherty-Clarke, Jeff Gelles, Pekka Lappalainen, Bruce L Goode
  [show abstract] [hide abstract]
  ABSTRACT: Cell locomotion and endocytosis are powered by the rapid polymerization and turnover of branched actin filament networks nucleated by Arp2/3 complex. Although a large number of cellular factors have been identified that stimulate Arp2/3 complex-mediated actin nucleation, only a small number of studies so far have addressed which factors promote actin network debranching. Here, we investigated the function of a conserved homolog of ADF/cofilin, glia maturation factor (GMF). We found that S. cerevisiae GMF (also called Aim7) localizes in vivo to cortical actin patches and displays synthetic genetic interactions with ADF/cofilin. However, GMF lacks detectable actin binding or severing activity and instead binds tightly to Arp2/3 complex. Using in vitro evanescent wave microscopy, we demonstrated that GMF potently stimulates debranching of actin filaments produced by Arp2/3 complex. Further, GMF inhibits nucleation of new daughter filaments. Together, these data suggest that GMF binds Arp2/3 complex to both "prune" daughter filaments at the branch points and inhibit new actin assembly. These activities and its genetic interaction with ADF/cofilin support a role for GMF in promoting the remodeling and/or disassembly of branched networks. Therefore, ADF/cofilin and GMF, members of the same superfamily, appear to have evolved to interact with actin and actin-related proteins, respectively, and to make mechanistically distinct contributions to the remodeling of cortical actin structures.
  Current biology: CB 03/2010; 20(9):861-7. · 10.99 Impact Factor
• Article: Structural basis and evolutionary origin of actin filament capping by twinfilin.

  Ville O Paavilainen, Maarit Hellman, Emmanuèle Helfer, Miia Bovellan, Arto Annila, Marie-France Carlier, Perttu Permi, Pekka Lappalainen
  [show abstract] [hide abstract]
  ABSTRACT: Dynamic reorganization of the actin cytoskeleton is essential for motile and morphological processes in all eukaryotic cells. One highly conserved protein that regulates actin dynamics is twinfilin, which both sequesters actin monomers and caps actin filament barbed ends. Twinfilin is composed of two ADF/cofilin-like domains, Twf-N and Twf-C. Here, we reveal by systematic domain-swapping/inactivation analysis that the two functional ADF-H domains of twinfilin are required for barbed-end capping and that Twf-C plays a critical role in this process. However, these domains are not functionally equivalent. NMR-structure and mutagenesis analyses, together with biochemical and motility assays showed that Twf-C, in addition to its binding to G-actin, interacts with the sides of actin filaments like ADF/cofilins, whereas Twf-N binds only G-actin. Our results indicate that during filament barbed-end capping, Twf-N interacts with the terminal actin subunit, whereas Twf-C binds between two adjacent subunits at the side of the filament. Thus, the domain requirement for actin filament capping by twinfilin is remarkably similar to that of gelsolin family proteins, suggesting the existence of a general barbed-end capping mechanism. Furthermore, we demonstrate that a synthetic protein consisting of duplicated ADF/cofilin domains caps actin filament barbed ends, providing evidence that the barbed-end capping activity of twinfilin arose through a duplication of an ancient ADF/cofilin-like domain.
  Proceedings of the National Academy of Sciences 03/2007; 104(9):3113-8. · 9.68 Impact Factor