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Roles of ADF/cofilin in actin polymerization and beyond.

Bamburg JR, Bernstein BW - F1000 Biol Rep (2010)

Bottom Line: In collaboration or competition with many other actin-binding proteins, the actin-depolymerizing factor/cofilins integrate transmembrane signals to coordinate the spatial and temporal organization of actin filament assembly/disassembly (dynamics).In addition, newly discovered effects of these proteins in lipid metabolism, gene regulation, and apoptosis suggest that their roles go well beyond regulating the cytoskeleton.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry and Molecular Biology, 1870 Campus Delivery, Colorado State University Fort Collins, CO 80523-1870 USA.

ABSTRACT
In collaboration or competition with many other actin-binding proteins, the actin-depolymerizing factor/cofilins integrate transmembrane signals to coordinate the spatial and temporal organization of actin filament assembly/disassembly (dynamics). In addition, newly discovered effects of these proteins in lipid metabolism, gene regulation, and apoptosis suggest that their roles go well beyond regulating the cytoskeleton.

No MeSH data available.


Concentration-dependent effects of cofilin on actin dynamics(a) Cofilin (purple) binds preferentially to ADP-actin (orange) and, at low stoichiometry with respect to actin subunits, severs filaments, creating new barbed and pointed ends. The cofilin dissociates with an actin subunit in the ADP form, and nucleotide exchange, enhanced by Srv2/CAP1 (exchange factor for actin-bound nucleotide when complexed to cofilin) and/or profilin (green), occurs on the actin. Cofilin can recycle to sever again. The pieces of filamentous actin (F-actin) generated can nucleate filament growth or can enhance depolymerization if assembly-competent ATP-actin is limiting. (b) At higher stoichiometry, cofilin binds to ADP-actin, but since binding is cooperative, regions of the F-actin become saturated and stabilized in the ‘twisted form’. Severing occurs rapidly, but as the cofilin is sequestered on the pieces of actin, severing is not persistent. Fragments are further depolymerized in the presence of actin-interacting protein 1 (Aip1) (blue) to generate monomer or can be used to nucleate growth. In cells under stress where ADP-actin levels are elevated, the cofilin-saturated F-actin assembles into rod-shaped bundles.
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fig-001: Concentration-dependent effects of cofilin on actin dynamics(a) Cofilin (purple) binds preferentially to ADP-actin (orange) and, at low stoichiometry with respect to actin subunits, severs filaments, creating new barbed and pointed ends. The cofilin dissociates with an actin subunit in the ADP form, and nucleotide exchange, enhanced by Srv2/CAP1 (exchange factor for actin-bound nucleotide when complexed to cofilin) and/or profilin (green), occurs on the actin. Cofilin can recycle to sever again. The pieces of filamentous actin (F-actin) generated can nucleate filament growth or can enhance depolymerization if assembly-competent ATP-actin is limiting. (b) At higher stoichiometry, cofilin binds to ADP-actin, but since binding is cooperative, regions of the F-actin become saturated and stabilized in the ‘twisted form’. Severing occurs rapidly, but as the cofilin is sequestered on the pieces of actin, severing is not persistent. Fragments are further depolymerized in the presence of actin-interacting protein 1 (Aip1) (blue) to generate monomer or can be used to nucleate growth. In cells under stress where ADP-actin levels are elevated, the cofilin-saturated F-actin assembles into rod-shaped bundles.

Mentions: Cofilin is best known as a regulator of actin filament non-equilibrium assembly/disassembly. Whether cofilin promotes actin assembly or disassembly depends upon the concentration of cofilin relative to actin and the relative concentrations of other actin-binding proteins [1,8]. In vitro studies have demonstrated that if the ratio of cofilin/actin subunits in a filament is low (less than 1%), this results in persistent filament severing (Figure 1) [8]. At higher cofilin/actin molar ratios (1:10 to 1:2), cofilin severs rapidly but transiently because it binds F-actin cooperatively and stabilizes F-actin in a twisted form as it saturates the severed pieces. Indeed, the assembly of the cofilin-ADP-actin complex into non-dynamic actin bundles (also called rods) is an important energy-conserving mechanism that in most cells is readily reversible (Figure 1); however, in axons and dendrites of stressed neurons, the rods block transport and cause loss of synapses [9], perhaps contributing to dementias, including Alzheimer disease [10].


Roles of ADF/cofilin in actin polymerization and beyond.

Bamburg JR, Bernstein BW - F1000 Biol Rep (2010)

Concentration-dependent effects of cofilin on actin dynamics(a) Cofilin (purple) binds preferentially to ADP-actin (orange) and, at low stoichiometry with respect to actin subunits, severs filaments, creating new barbed and pointed ends. The cofilin dissociates with an actin subunit in the ADP form, and nucleotide exchange, enhanced by Srv2/CAP1 (exchange factor for actin-bound nucleotide when complexed to cofilin) and/or profilin (green), occurs on the actin. Cofilin can recycle to sever again. The pieces of filamentous actin (F-actin) generated can nucleate filament growth or can enhance depolymerization if assembly-competent ATP-actin is limiting. (b) At higher stoichiometry, cofilin binds to ADP-actin, but since binding is cooperative, regions of the F-actin become saturated and stabilized in the ‘twisted form’. Severing occurs rapidly, but as the cofilin is sequestered on the pieces of actin, severing is not persistent. Fragments are further depolymerized in the presence of actin-interacting protein 1 (Aip1) (blue) to generate monomer or can be used to nucleate growth. In cells under stress where ADP-actin levels are elevated, the cofilin-saturated F-actin assembles into rod-shaped bundles.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2990448&req=5

fig-001: Concentration-dependent effects of cofilin on actin dynamics(a) Cofilin (purple) binds preferentially to ADP-actin (orange) and, at low stoichiometry with respect to actin subunits, severs filaments, creating new barbed and pointed ends. The cofilin dissociates with an actin subunit in the ADP form, and nucleotide exchange, enhanced by Srv2/CAP1 (exchange factor for actin-bound nucleotide when complexed to cofilin) and/or profilin (green), occurs on the actin. Cofilin can recycle to sever again. The pieces of filamentous actin (F-actin) generated can nucleate filament growth or can enhance depolymerization if assembly-competent ATP-actin is limiting. (b) At higher stoichiometry, cofilin binds to ADP-actin, but since binding is cooperative, regions of the F-actin become saturated and stabilized in the ‘twisted form’. Severing occurs rapidly, but as the cofilin is sequestered on the pieces of actin, severing is not persistent. Fragments are further depolymerized in the presence of actin-interacting protein 1 (Aip1) (blue) to generate monomer or can be used to nucleate growth. In cells under stress where ADP-actin levels are elevated, the cofilin-saturated F-actin assembles into rod-shaped bundles.
Mentions: Cofilin is best known as a regulator of actin filament non-equilibrium assembly/disassembly. Whether cofilin promotes actin assembly or disassembly depends upon the concentration of cofilin relative to actin and the relative concentrations of other actin-binding proteins [1,8]. In vitro studies have demonstrated that if the ratio of cofilin/actin subunits in a filament is low (less than 1%), this results in persistent filament severing (Figure 1) [8]. At higher cofilin/actin molar ratios (1:10 to 1:2), cofilin severs rapidly but transiently because it binds F-actin cooperatively and stabilizes F-actin in a twisted form as it saturates the severed pieces. Indeed, the assembly of the cofilin-ADP-actin complex into non-dynamic actin bundles (also called rods) is an important energy-conserving mechanism that in most cells is readily reversible (Figure 1); however, in axons and dendrites of stressed neurons, the rods block transport and cause loss of synapses [9], perhaps contributing to dementias, including Alzheimer disease [10].

Bottom Line: In collaboration or competition with many other actin-binding proteins, the actin-depolymerizing factor/cofilins integrate transmembrane signals to coordinate the spatial and temporal organization of actin filament assembly/disassembly (dynamics).In addition, newly discovered effects of these proteins in lipid metabolism, gene regulation, and apoptosis suggest that their roles go well beyond regulating the cytoskeleton.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry and Molecular Biology, 1870 Campus Delivery, Colorado State University Fort Collins, CO 80523-1870 USA.

ABSTRACT
In collaboration or competition with many other actin-binding proteins, the actin-depolymerizing factor/cofilins integrate transmembrane signals to coordinate the spatial and temporal organization of actin filament assembly/disassembly (dynamics). In addition, newly discovered effects of these proteins in lipid metabolism, gene regulation, and apoptosis suggest that their roles go well beyond regulating the cytoskeleton.

No MeSH data available.