We study eukaryotic cell behavior with a focus on the organization and regulation of the microfilament system – a force generating machinery of proteins with actin as principal component. As an intimate component of the cell periphery, the microfilament system responds to receptor activation by forming surface-protruding actin containing processes used for substrate adhesions, contacts with other cells and for migration. It mediates intracellular movements of vesicles and macromolecular complexes, and actin and actin-binding proteins also function in different nuclear processes. Profilin is an actin-binding protein which together with the non-muscle actin isoforms has been under our study for nearly three decades. It controls actin polymerization through the docking of profilin:actin complexes to protein machineries like WASP/Wave, Ena/VASP and members of the formin family of proteins. Thus profilin is important for the fine-tuning and regulation in time and space of actin polymerization, for instance during formation of protruding lamellipodia and filopodia at advancing cell edges. Profilin also binds the phosphoinositide lipids PIP2 and PIP3 further emphasizing the close association to plasma membrane associated receptor signaling. The connection of the microfilament system with cell signaling, growth control, adhesion and migration explains why cancer cells often display changes in microfilament organization and actin regulatory components.
Our current focus is on how profilin:actin is brought to polymer-forming sites at the cell edge, the distribution of profilin mRNA and how profilin and actin enters the cell nucleus and what their role might be in this compartment. For this we combine biochemical analyses with molecular cell biology and imaging techniques.
Selected Publications
The profilin:actin complex localizes to sites of dynamic actin polymerization at the leading edge of migrating cells and pathoge
Li Y, Grenklo S, Higgins T, Karlsson R
Eur J Cell Biol. 87:893-904, 2008.
The microfilament system and malignancy.
Lindberg U, Karlsson R, Lassing I, Schutt CE, Höglund AS
Semin Cancer Biol. 18:2-11, 2008.
Profilin, an essential control element for actin polymerization
Karlsson R and Lindberg U. In Actin Monomer-binding Proteins. Editor: Pekka Lappalainen, Landes Bioscience and Springer Science and Business Media, 2007.
A crucial role for profilin-actin in the intracellular motility of Listeria monocytogenes.
Grenklo S, Geese M, Lindberg U, Wehland J, Karlsson R, Sechi AS.
EMBO Rep. 4:523-9, 2003.
Profilin I colocalizes with speckles and Cajal bodies: a possible role in pre-mRNA splicing.
Skare P, Kreivi JP, Bergström A, Karlsson R.Exp Cell Res. 286:12-21, 2003.
Visualization of the peripheral weave of microfilaments in glia cells.
Höglund AS, Karlsson R, Arro E, Fredriksson BA, Lindberg U.
J Muscle Res Cell Motility. 1:127-46, 1980.
