Coordinated polymerization of actin filaments against membrane provides force for generation of plasma membrane protrusions and invaginations during cell morphogenesis, motility, and endocytosis. In addition, actin filaments together with myosin II filaments form contractile structures, which provide the force for muscle contraction, and have an important role in morphogenesis and mechanosensing of non-muscle cells. Abnormalities in actin-dependent processes, including cell morphogenesis, motility and cytokinesis, often occur in cancer cells. Furthermore, many pathogens exploit the actin polymerization machinery of the host cell during the infection process. Thus, elucidating the mechanisms of actin dynamics will be valuable for understanding the principles of these actin-dependent pathological states.

Our group uses an array of biochemical, biophysical, cell biological, and genetic methods to uncover how structure and dynamics of the actin cytoskeleton are regulated in various cellular processes.


The organization and dynamics of the actin cytoskeleton are regulated by a plethora of actin-binding proteins, which interact with monomeric and/or filamentous actin to control different aspects of actin dynamkcs. Whereas actin filament nucleation and polymerization have been extensively studied, the mechanisms underlying actin filament disassembly and recycling of actin monomers for new rounds of polymerization are less well understood. Twinfilin and cyclase-associated-protein (CAP, also known as Srv2 in budding yeast) are evolutionarily conserved proteins that contribute to actin filament disassembly and monomer recycling. However, the exact mechanisms by which twinfilin and CAP associate with actin and their other interaction partners as well as the roles of these proteins in actin dynamics in cells are incompletely understood. Importantly, altered expression levels of twinfilin and CAP are also linked to many malignant cancers, and thus elucidating the cellular functions of these proteins will also provide insights into the mechanisms of cancer cell invasion and metastasis.

Twinfilin is an actin monomer binding protein, which is composed of two actin-depolymerization factor homology (ADF-H) domains. In addition to actin monomers, twinfilin interacts with filament barbed ends, cyclase-associated protein, and heterodimeric capping protein. However, its exact role in actin dynamics is not understood. We apply a wide array of biochemical, cell biological and genetic methods to elucidate how the different activities of twinfilin contribute to its function in mammalian cells. We also aim to reveal how the activity and localization of twinfilin are regulated in normal and malignant cells.
Cyclase-associated protein is a central regulator of cytoskeletal dynamics in all eukaryotes. It interacts with actin monomers as well as with the actin monomer-binding proteins profilin, ADF/cofilin, and twinfilin. We use biochemical, cell biological and structural methods to unravel the mechanisms by which cyclase-associated-protein, together with ADF/cofilin, twinfilin and profilin, promotes rapid actin dynamics. In addition, we examine how the activity and localization of CAP are regulated in mammalian cells, and how it contributes to cytoskeletal dynamics in cultured cells and in a tissue environment.


The activities of many actin-binding proteins are regulated by PI(4,5)P2 in vitro. However, the structural mechanisms and possible physiological relevancies of these interactions are largely unknown. Furthermore, many actin cytoskeleton associated proteins, such as the BAR domain family proteins, can directly sense and generate membrane curvature to generate plasma membrane protrusions and invaginations in collaboration with the actin cytoskeleton.

Mechanism and biological roles of actin-binding protein – PI(4,5)P2 interactions

The activities of many actin-binding proteins, can be regulated by membrane phosphoinositides. Typically those proteins that induce actin filament assembly or link the actin cytoskeleton to the plasma membrane are up-regulated by phosphoinositides, whereas proteins promoting actin filament disassembly are inhibited by membrane phospholipids. Consequently, an increase in the plasma membrane phosphoinositide (especially PI(4,5)P2 and PI(3,4,5)P3) levels promotes actin filament assembly at the membranes. However, the molecular mechanisms by which various actin-binding proteins associate with phosphoinositide-rich membranes as well as the physiological roles of these interactions have remained elusive. We use a wide array of biochemical, biophysical, and cell biological approaches to reveal how central actin-binding proteins associate with PI(4,5)P2-rich in vitro and in cells.

Coordinating actin and plasma membrane dynamics by the I-BAR family proteins

MIM (missing-in-metastasis), IRSp53, ABBA, IRTKS and Pinkbar are mammalian proteins that function at the interface between plasma membrane and the actin cytoskeleton. These proteins harbor an N-terminal membrane-binding I-BAR domain and interact with monomeric actin through their C-terminal WH2 domains. The I-BAR domain can both sense and generate negative membrane curvature, but the biological roles of this membrane interaction activity are not known. We use a combination of proteomics, genetics and cell biological approaches to elucidate the cellular and physiological roles of I-BAR proteins, and to reveal how the membrane curvature sensing/generating activity of these proteins is linked to actin dynamics.


In addition to protrusive actin filament arrays that provide force for cellular processes involving membrane dynamics, many cell-types also possess contractile actomyosin bundles. These include myofibrils of muscle cells and stress fibers of non-muscle cells. Stress fibers contribute to cell adhesion, morphogenesis and migration. Interestingly, stress fibers are mechanosensitive structures; i.e. they only form on stiff matrix and align along external force in cells. However, the mechanisms by which myofibrils and stress fibers are assembled in cells, and how myosin II is recruited to these structures are currently poorly understood.

Stress fibers

Our studies on stress fibers of U2OS cells shed light on the mechanisms by which contractile actomyosin bundles are assembled in mesenchymal cells. However, many central questions concerning this process remain unanswered. We do not for example know how myosin II is specifically recruited to stress fiber precursors, and why multiple actin filament populations are required for stress fiber assembly. Moreover, how different actin filament populations associate with each other during stress fiber assembly, and the mechanisms by which stress fibers are linked to the plasma membrane are unknown. Finally, the mechanosensitive pathways controlling the assembly and alignment of stress fibers are incompletely understood. Thus, we apply a combination of cell biological, genetic and biochemical approaches to answer to these questions.

Cardiomyocyte sarcomeres

In contrast to non-muscle cells, where most actin filaments are highly dynamic, the actin filaments in muscle sarcomeres are believed to be relatively stable. However, despite the predicted slow actin filament turnover, many proteins that play central roles in promoting actin dynamics in non-muscle cells are also expressed in muscle cells. We use cultured cardiomyocytes to examine the mechanisms of actin dynamics in muscle sarcomeres. Of our special interest is to elucidate the mechanism by which myofibrils are formed in developing muscle cells, and to reveal how various actin-binding proteins contribute this process.



Text for YPJ forms

Our group consist of PI, 4 post-docs, 6 PhD-students and a technician. We apply an array of biochemical, biophysical, cell biological, and genetic methods to reveal how structure and dynamics of the actin cytoskeleton are regulated in various cellular processes.


Contact info

Mailing address:
Biocenter 2, room 2016
Viikinkaari 5D, 00790 Helsinki, Finland
Pekka Lappalainen tel: +358-50-4155433
Lab: +358-50-4484609
All e-mails:
firstname.lastname -at-

University of Helsinki