Actin disassembly by cofilin, coronin, and Aip1 occurs in bursts and is inhibited by barbed-end cappers.
Turnover of actin filaments in cells requires rapid actin disassembly in a cytoplasmic environment that thermodynamically favors assembly because of high concentrations of polymerizable monomers. We here image the disassembly of single actin filaments by cofilin, coronin, and actin-interacting protein 1, a purified protein system that reconstitutes rapid, monomer-insensitive disassembly (Brieher, W.M., H.Y. Kueh, B.A. Ballif, and T.J. Mitchison. 2006. J. Cell Biol. 175:315-324). In this three-component system, filaments disassemble in abrupt bursts that initiate preferentially, but not exclusively, from both filament ends. Bursting disassembly generates unstable reaction intermediates with lowered affinity for CapZ at barbed ends. CapZ and cytochalasin D (CytoD), a barbed-end capping drug, strongly inhibit bursting disassembly. CytoD also inhibits actin disassembly in mammalian cells, whereas latrunculin B, a monomer sequestering drug, does not. We propose that bursts of disassembly arise from cooperative separation of the two filament strands near an end. The differential effects of drugs in cells argue for physiological relevance of this new disassembly pathway and potentially explain discordant results previously found with these drugs.
Kueh
Hao Yuan
HY
Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.
Charras
Guillaume T
GT
Mitchison
Timothy J
TJ
Brieher
William M
WM
D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000378:metabolism; D008841:Actin Cytoskeleton / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D000199:Actins / Q000378:metabolism*; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D051347:CapZ Actin Capping Protein / Q000378:metabolism; D002352:Carrier Proteins; D002460:Cell Line; D002522:Chlorocebus aethiops; D051338:Cofilin 1 / Q000378:metabolism*; D015638:Cytochalasin D / Q000494:pharmacology; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D051528:Guanylate Kinases; D000882:Haplorhini; D006367:HeLa Cells; D006801:Humans; D008840:Microfilament Proteins / Q000378:metabolism*; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D011506:Proteins / Q000378:metabolism*; D011817:Rabbits; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D053778:Thiazolidines / Q000494:pharmacology; D054378:Acetogenins
D015107:4-Butyrolactone; D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D019086:Bridged Bicyclo Compounds, Heterocyclic; D051347:CapZ Actin Capping Protein; D002352:Carrier Proteins; D051338:Cofilin 1; D015638:Cytochalasin D; D051528:Guanylate Kinases; D008840:Microfilament Proteins; D019384:Nucleic Acid Synthesis Inhibitors; D011506:Proteins; D053778:Thiazolidines; C495810:CFL1 protein, human; C118067:WDR1 protein, human; C438920:coronin acetogenin; D054378:Acetogenins; C485777:MAGI2 protein, human; C037068:latrunculin B