INF2: Lysates

Actin filaments grow only when actin monomers have access to the fast-growing barbed end of the filament. The geometry of the filament network depends on the actions of the ARP2/3 complex (MIM 604221) and members of the formin family, such as INF2. The ARP2/3 complex binds to the sides of preexisting filaments and nucleates filaments whose barbed ends are quickly blocked by capping proteins, producing brush-like structures, such as those found at the leading edges of crawling cells. In contrast, formins bind to the barbed ends of growing filaments and protect them from capping, creating long filaments that can be cross-linked into bundles, such as those found in actin cables of yeast. Interaction of formins with actin barbed ends occurs through the formin homology-2 (FH2) domain. FH2 domains accelerate filament nucleation, move with the barbed end as the filament grows, and block capping of the barbed end by proteins such as gelsolin (GSN; MIM 137350). The FH1 domain of formins binds to profilin (see MIM 176610) and accelerates elongation from the FH2-bound barbed ends (Bindschadler and McGrath, 2004 [PubMed 15466701]; Chhabra and Higgs, 2006 [PubMed 16818491]).[supplied by OMIM]