Continuous membrane-cytoskeleton adhesion requires continuous accommodation to lipid and cytoskeleton dynamics

The plasma membrane of most animal cells conforms to the cytoskeleton and only occasionally separates to form blebs. Previous studies indicated that many weak interactions between cytoskeleton and the lipid bilayer kept the surfaces together to counteract the normal outward pressure of cytoplasm. Either the loss of adhesion strength or the formation of gaps in the cytoskeleton enables the pressure to form blebs. Membrane-associated cytoskeleton proteins, such as spectrin and filamin, can control the movement and aggregation of membrane proteins and lipids, e.g., phosphoinositol phospholipids (PIPs), as well as blebbing. At the same time, lipids (particularly PIPs) and membrane proteins affect cytoskeleton and signaling dynamics. We consider here the roles of the major phosphatidylinositol-4,5-diphosphate (PIP2) binding protein, MARCKS, and PIP2 levels in controlling cytoskeleton dynamics. Further understanding of dynamics will provide important clues about how membrane-cytoskeleton adhesion rapidly adjusts to cytoskeleton and membrane dynamics.