Current model for blebbing signaling.

<p>(A) The results of our present study indicate that microtubules can be positioned upstream of bleb extension. In the presence of microtubules, PIP3 localizes to the anterior membrane and induces lamellipodia formation by enhancing the assembly of actin at that location. Without microtubules, PIP3 delocalizes from the cell membrane. PIP2 recruits myosin II along the cortex, generating more internal pressure inside of the cell. A bleb will extend at the weakest part of the cortex (where the levels of PIP2 and myosin II proteins are low) because myosin II contributes to the rigidity of the cortex. (B) A model of lamellipodium and bleb extension in uncut cells. When microtubules extend to the cortex, unknown signals are conveyed along the microtubules that locally induce PIP3 accumulation and actin assembly in the cortex, resulting in the extension of lamellipodium (left). However, when microtubules retract or detach from the cortex, PIP3 delocalizes from the cortex. In the presence of intracellular pressure, based on the power of myosin II, the cell membrane detaches from the weakest part of the actin cortex, resulting in bleb formation. Blue double arrows, myosin II; red, actin filaments; green, PIP3.