Live-cell Imaging and Analysis Reveal the Molecular Mechanism of Membrane Blebbing

Abstract

Plasma membrane is associated with the underlying actin filaments. When the intracellular pressure increased or the actin filaments are locally disrupted, the membrane protrudes. This spherical membrane protrusion is called membrane blebs. Membrane blebs are often observed during cytokinesis and cell migration. Blebs regress when the actin cytoskeleton re-accumulates under the plasma membrane. However, it remains unclear how bleb expansion and retraction are regulated. In our previous study, we addressed this issue by using live imaging and demonstrated that the interplay between two small GTPases, Rnd3 and RhoA, is important for the establishment of bleb cycle. Recently, we report that the cytoplasmic fluidity is regulated in the blebbing cells; the cytoplasm of rapidly expanding membrane blebs is more disordered than the cytoplasm of retracting blebs. The increase of cytoplasmic fluidity in the expanding bleb is caused by a sharp rise in the calcium concentration. The STIM1-Orai1 pathway regulates this rapid and restricted increase of calcium in the expanding blebs. In this review, we focus on the molecular mechanism controlling cytoplasmic fluidity that enables dynamic morphological changes during membrane blebbing.