Purpose of review
This article discusses recent advances and unsolved questions in our understanding of actin filament organization and dynamics in the red blood cell (RBC) membrane skeleton, a two-dimensional quasi-hexagonal network consisting of (α1β1)2-spectrin tetramers interconnecting short actin filament-based junctional complexes.
In contrast to the long-held view that RBC actin filaments are static structures that do not exchange subunits with the cytosol, RBC actin filaments are dynamic structures that undergo subunit exchange and turnover, as evidenced by monomer incorporation experiments with rhodamine-actin and filament disruption experiments with actin-targeting drugs. The malaria-causing parasite, Plasmodium falciparum, co-opts RBC actin dynamics to construct aberrantly branched actin filament networks. Even though RBC actin filaments are dynamic, RBC actin filament lengths are highly uniform (∼37 nm). RBC actin filament lengths are thought to be stabilized by the capping proteins, tropomodulin-1 and αβ-adducin, as well as the side-binding protein tropomyosin, present in an equimolar combination of two isoforms, TM5b (Tpm1.9) and TM5NM1 (Tpm3.1).
New evidence indicates that RBC actin filaments are not simply passive cytolinkers, but rather dynamic structures whose assembly and disassembly play important roles in RBC membrane function.