A protein called actin forms filamentous structures within cells. When these structures elongate, they push the plasma membrane of the cell forward. This elongation process gives animal cells the ability to generate finger-like membrane protrusions. These protrusions drive cell migration or formation of specific structures on the surface of the cell, which are then harnessed by the cell to change its shape.
A large number of different proteins control elongation and disassembly of actin filaments. Many of these proteins also interact with the plasma membrane. Defects in this finely tuned system are linked to many disease processes, such as cancer invasion.
Researchers at the University of Helsinki have now discovered that different proteins that regulate actin filaments show enormous differences in the way they interact with the plasma membrane.
"They also differ a lot in the mechanisms they use to sense lipids in the membrane. Actually, these proteins can touch simultaneously several lipid molecules, and depending on the actin-binding protein, these interactions may be very transient or amazingly stable," says post-doctoral fellow Yosuke Senju from the Pekka Lappalainen lab at the Institute of Biotechnology, University of Helsinki.
The researchers noticed that these differences precisely correlate with the specific functions of these proteins in cytoskeletal dynamics.
Post-doctoral fellow Maria Kalimeri from the Ilpo Vattulainen lab at the Department of Physics also combined these biochemical data with computer simulations to uncover the precise atomic mechanisms through which actin-binding proteins associate with plasma membranes.
Yosuke Senju, Maria Kalimeri, Essi V. Koskela, Pentti Somerharju, Hongxia Zhao, Ilpo Vattulainen and Pekka Lappalainen. Mechanistic principles underlying regulation of the actin cytoskeleton by phosphoinositides. PNAS vol. 114 no. 43, doi: 10.1073/pnas.1705032114