Beyond pore formation: reorganization of the plasma membrane induced by pore-forming proteins

Pore-forming proteins (PFPs) are a heterogeneous group of proteins that are expressed and secreted by a wide range of organisms. PFPs are produced as soluble monomers that bind to a receptor molecule in the host cell membrane. They then assemble into oligomers that are incorporated into the lipid membrane to form transmembrane pores. Such pore formation alters the permeability of the plasma membrane and is one of the most common mechanisms used by PFPs to destroy target cells. Interestingly, PFPs can also indirectly manipulate diverse cellular functions. In recent years, increasing evidence indicates that the interaction of PFPs with lipid membranes is not only limited to pore-induced membrane permeabilization but is also strongly associated with extensive plasma membrane reorganization. This includes lateral rearrangement and deformation of the lipid membrane, which can lead to the disruption of target cell function and finally death. Conversely, these modifications also constitute an essential component of the membrane repair system that protects cells from the lethal consequences of pore formation. Here, we provide an overview of the current knowledge on the changes in lipid membrane organization caused by PFPs from different organisms.