Regulation of actin assembly by inositol phospholipids

COLL 39

Paul A Janmey, Wujing Xian, Robert Buck, and Makoto Funaki. Institute for Medicine and Engineering, University of Pennsylvania, 3340 Smith Walk, Philadelphia, PA 19104
Cellular assembly of actin filaments is regulated by polyphosphoinositides (PPIs).   Proteins such as N-WASP and alpha-actinin that promote actin assembly or crosslinking are activated by PPIs, and others like gelsolin or cofilin that disassemble actin filaments are inhibited by PPIs.  The net effect of these interactions leads to increased actin assembly when PPI levels increase, and disassembly when PPIs are removed by hydrolysis.  Predictions from in vitro studies are confirmed by studies of intact cells where addition of a cell-permeant gelsolin peptide derivative with affinity for PIP2 disrupts actin assembly in a reversible manner  and blocks functions that require actin assembly.  Binding of PPIs to target cytoskeletal proteins like gelsolin depends strongly on local membrane features like curvature and lateral sequestration suggesting how specificity of binding events can be enhanced by physical properties of the membrane.