Actin filaments (F-actin) are composed of actin subunits. The dissociation of actin monomers can occur from either end of F-actin. The rate of dissociation is faster from the minus-end or the pointed end, where the actin subunits exist with a bound ADP, together known as ADP-actin. The depolymerization of F-actin is aided by proteins, including the actin-depolymerizing factor (ADF) and cofilin family of proteins, gelsolin, and glia maturation factor (GMF).
In F-actin, the ADF/cofilin proteins can bind with ADP-actins in a one-to-one ratio. The actin filament twists when these proteins bind to ADP-actin, generating mechanical stress and making the filament brittle. This stress allows rapid dissociation of the cofilin bound-ADP-G-actins from the filament. The ADF/cofilin proteins are also associated with AIP-1 (actin-interacting protein1), further enhancing the dissociation rate on the minus-end.
Gelsolin is a calcium ion-activated actin-binding protein. Activated gelsolin wedges into a straight actin filament and disrupts the interactions between the actin monomers within the filament, splitting the F-actin into two. One end has a newly formed gelsolin-capped plus-end, while the other filament has a newly formed minus-end with rapidly dissociating ADP-G-actins.
The disassembly of actin filaments can also occur at branched filaments bound to the Arp2/3 complex. GMF binds to the Arp2/3 complex at the branch junction of actin networks. Upon binding, it prevents further nucleation of actin filaments from that site. GMF plays an important role in the lamellipodia formation required for cell movement and migration.
Actin filament disassembly is guided by proteins like Cofilin and Gelsolin through distinct mechanisms.
Cofilin, a small protein, binds in a one-on-one ratio with ADP-actin subunits at the F-actin minus-end. As a result, the F-actin twists, reducing the length of each helical turn.
The shrinking F-actin helices generate mechanical stress, increasing the rate of ATP hydrolysis, which makes the filament brittle. This, in turn, eases the release of ADP-actin monomers from the minus-end.
Gelsolin is a multidomain protein regulated by the calcium ion concentration in the cell. With the binding of calcium ions, Gelsolin undergoes a conformational change that allows it to attach to the sides of F-actin.
Upon binding to the sides of F-actin, the activated Gelsolin-calcium inserts itself between actin subunits in the filament, wedging apart the monomers to form a Gelsolin-actin complex.
As a result, the actin filament breaks into two, where one part has a Gelsolin-Calcium capped plus-end and a minus-end with rapidly dissociating ADP-actins.
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