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Actin-binding proteins regulate assembly and disassembly of actin filaments. Cofilin, a member of the ADF/cofilin family is actually a protein with 70% sequence homology to ADF, making it part of the ADF/cofilin family of small ADP-binding proteins . The protein binds to actin monomers and filaments, G actin and F actin, respectively. Cofilin causes depolymerization at the minus end of filaments, thereby preventing their reassembly. The protein is known to sever actin filaments by creating more positive ends on filament fragments. Cofilin/ADF(destrin) is likely to sever F-actin without capping  and prefers ADP-actin. These monomers can be recycled by profilin, activating monomers to go back into filament form again by an ADP-to-ATP exchange. ATP-actin is then available for assembly .
Additional recommended knowledge
Cofilin alters F-actin structure to make it twisted. The structure is a helix, proposed to bind G-actin. ADF/Destrin fits better with a twist in F-actin between two actin subunits (see figure above). The levels of cofilin are shown in 'd' above. 4 indicates 40% and 1 indicates 10% by volume of cofilin. The silver portion of image 'd' is actin. The cofilin binding site includes subdomain 2. The twist in the structure causes strain at the actin-actin contact site. Four actin histidines near the cofilin binding site may be needed for cofilin/actin interaction, but pH sensitivity alone may not be enough of an explanation for the levels of interaction encountered. Cofilin is accommodated in ADP-F actin because of increased flexibility in this form of actin. Binding by both cofilin and ADF(destrin) causes the crossover length of the filament to be reduced. Therefore, strains increase filament dynamics and the level of filament fragmentation observed.
Cofilin is a ubiquitous actin-binding factor required for the reorganization of actin filaments. ADF/Cofilin family members bind G-actin monomers and depolymerize actin filaments through two mechanisms: severing and increasing off-rate for actin monomers from the pointed end. "Older" ADP/ADP-Pi actin filaments free of tropomyosin and proper pH are required for cofilin to function effectively. In the presence of readily available ATP-G-actin cofilin speeds-up actin polymerization via its actin-severing activity (providing free barbed ends for furtherer polymerization and nucleation by Arp2/3 complex). As a long-lasting in vivo effect, cofilin recycles older ADP-F-actin, helping cell to maintain ATP-G-actin pool for sustained motlity. pH, phosphorylation and phosphoinositides regulate cofilin’s binding and associating activity with actin
What Cofilin Functions with
The Arp2/3 complex and cofilin work together to reorganize the actin filaments in the cytoskeleton. Arp 2/3, an actin binding proteins complex, binds to the side of ATP-F-actin near the growing barbed end of the filament, causing nucleation of a new F-actin branch, while cofilin-driven depolymerization takes place after dissociating from the Arp2/3 complex. They also work together to reorganize microtubules in order to traffic more proteins by vesicle to continue the growth of filaments.
Cofilin also binds with other proteins such as myosin, tropomyosin, α-actinin, gelsolin and scruin. These proteins compete with cofilin for actin binding.cofilin also play role in innate immune response
In a Model Organism
ADF/cofilins are found in ruffling membranes and at the leading edge of mobile cells. In particular, ADF/cofilin promotes disassembly of the filament at the rear of the brush in Xenopus laevis lamellipodia, a protrusion from fibroblast cells characterized by actin networks. Subunits are added to barbed ends and lost from rear-facing pointed ends. Increasing the rate constant, k, for actin dissociation from the pointed ends was found to sever actin filaments. Through this experimentation, it was found that ATP or ADP-Pi are probably involved in binding to actin filaments.
|This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Cofilin". A list of authors is available in Wikipedia.|