actin depolymerizing factors


Summary: A family of low MOLECULAR WEIGHT actin-binding proteins found throughout eukaryotes. They remodel the actin CYTOSKELETON by severing ACTIN FILAMENTS and increasing the rate of monomer dissociation.

Top Publications

  1. Zhang C, Guo L, Wang X, Zhang H, Shi H, Xu W, et al. Molecular characterization of four ADF genes differentially expressed in cotton. J Genet Genomics. 2007;34:347-54 pubmed
  2. Racz B, Weinberg R. Spatial organization of cofilin in dendritic spines. Neuroscience. 2006;138:447-56 pubmed
    ..These data suggest that cofilin may link synaptic plasticity to the actin remodeling that underlies changes in spine morphology. ..
  3. FLYNN K, Hellal F, Neukirchen D, Jacob S, Tahirovic S, Dupraz S, et al. ADF/cofilin-mediated actin retrograde flow directs neurite formation in the developing brain. Neuron. 2012;76:1091-107 pubmed publisher
    ..Our data reveal how ADF/Cofilin organizes the cytoskeleton to drive actin retrograde flow and thus break the spherical shape of neurons. ..
  4. Bernstein B, Shaw A, Minamide L, Pak C, Bamburg J. Incorporation of cofilin into rods depends on disulfide intermolecular bonds: implications for actin regulation and neurodegenerative disease. J Neurosci. 2012;32:6670-81 pubmed publisher
    ..Oligomerization of cofilin in cells represents one more mechanism for regulating the actin dynamizing activity of cofilin and probably underlies synaptic loss. ..
  5. Nishimura Y, Yoshioka K, Bernard O, Bereczky B, Itoh K. A role of LIM kinase 1/cofilin pathway in regulating endocytic trafficking of EGF receptor in human breast cancer cells. Histochem Cell Biol. 2006;126:627-38 pubmed
    ..Taken together, our novel findings presented in this paper implicate that LIMK1 signaling indeed plays a pivotal role in the regulation of EGFR trafficking through the endocytic pathway in invasive tumor cells. ..
  6. Wiggan O, Shaw A, DeLuca J, Bamburg J. ADF/cofilin regulates actomyosin assembly through competitive inhibition of myosin II binding to F-actin. Dev Cell. 2012;22:530-43 pubmed publisher
  7. van Rheenen J, Song X, van Roosmalen W, Cammer M, Chen X, DesMarais V, et al. EGF-induced PIP2 hydrolysis releases and activates cofilin locally in carcinoma cells. J Cell Biol. 2007;179:1247-59 pubmed
    ..Moreover, our data provide evidence for how PLC is involved in the formation of protrusions in breast carcinoma cells during chemotaxis and metastasis towards EGF. ..
  8. Frantz C, Barreiro G, Dominguez L, Chen X, Eddy R, Condeelis J, et al. Cofilin is a pH sensor for actin free barbed end formation: role of phosphoinositide binding. J Cell Biol. 2008;183:865-79 pubmed publisher
    ..In contrast, phosphoinositide binding by cofilin-H133A is attenuated and pH insensitive. These data suggest a molecular mechanism whereby cofilin acts as a pH sensor to mediate a pH-dependent actin filament dynamics. ..
  9. Jimenez Baranda S, Gomez Mouton C, Rojas A, Martinez Prats L, Mira E, Ana Lacalle R, et al. Filamin-A regulates actin-dependent clustering of HIV receptors. Nat Cell Biol. 2007;9:838-46 pubmed
    ..Our results thus identify filamin-A as an adaptor protein that links HIV-1 receptors to the actin cytoskeleton remodelling machinery, which may facilitate virus infection. ..

More Information


  1. Brieher W, Kueh H, Ballif B, Mitchison T. Rapid actin monomer-insensitive depolymerization of Listeria actin comet tails by cofilin, coronin, and Aip1. J Cell Biol. 2006;175:315-24 pubmed
    ..The cooperative activities of cofilin, coronin, and Aip1 should provide a biochemical basis for understanding how actin filaments can grow in some places in the cell while shrinking in others. ..
  2. Carlisle H, Manzerra P, Marcora E, Kennedy M. SynGAP regulates steady-state and activity-dependent phosphorylation of cofilin. J Neurosci. 2008;28:13673-83 pubmed publisher
    ..Our data show that synGAP mediates a rate-limiting step in steady-state regulation of spine morphology and in transient NMDA-receptor-dependent regulation of the spine cytoskeleton. ..
  3. van Rheenen J, Condeelis J, Glogauer M. A common cofilin activity cycle in invasive tumor cells and inflammatory cells. J Cell Sci. 2009;122:305-11 pubmed publisher
  4. Kaji N, Muramoto A, Mizuno K. LIM kinase-mediated cofilin phosphorylation during mitosis is required for precise spindle positioning. J Biol Chem. 2008;283:4983-92 pubmed
    ..Our results suggest that LIMK1-mediated cofilin phosphorylation is required for accurate spindle orientation by stabilizing cortical actin networks during mitosis. ..
  5. Hsieh S, Ferraro G, Fournier A. Myelin-associated inhibitors regulate cofilin phosphorylation and neuronal inhibition through LIM kinase and Slingshot phosphatase. J Neurosci. 2006;26:1006-15 pubmed
    ..We speculate that SSH-mediated persistent cofilin activation may be responsible for maintaining an inhibited neuronal phenotype in response to myelin inhibitors. ..
  6. Bamburg J, Bloom G. Cytoskeletal pathologies of Alzheimer disease. Cell Motil Cytoskeleton. 2009;66:635-49 pubmed publisher
    ..Cell Motil. Cytoskeleton, 2009. (c) 2009 Wiley-Liss, Inc. ..
  7. Pfaendtner J, De La Cruz E, Voth G. Actin filament remodeling by actin depolymerization factor/cofilin. Proc Natl Acad Sci U S A. 2010;107:7299-304 pubmed publisher
  8. Barisic S, Nagel A, Franz Wachtel M, Macek B, Preiss A, Link G, et al. Phosphorylation of Ser 402 impedes phosphatase activity of slingshot 1. EMBO Rep. 2011;12:527-33 pubmed publisher
    ..We thus identify a universal mechanism by which PKD controls SSH1 phosphatase activity. ..
  9. Spratley S, Bastea L, Döppler H, Mizuno K, Storz P. Protein kinase D regulates cofilin activity through p21-activated kinase 4. J Biol Chem. 2011;286:34254-61 pubmed publisher
    ..The regulation of cofilin activity at multiple levels may explain the inhibitory effects of PKD on barbed end formation as well as on directed cell migration. ..
  10. Fan J, Saunders M, Haddadian E, Freed K, De La Cruz E, Voth G. Molecular origins of cofilin-linked changes in actin filament mechanics. J Mol Biol. 2013;425:1225-40 pubmed publisher
    ..These results reveal the molecular origins of cofilin-dependent changes in actin filament mechanics that may promote filament severing. ..
  11. Song X, Chen X, Yamaguchi H, Mouneimne G, Condeelis J, Eddy R. Initiation of cofilin activity in response to EGF is uncoupled from cofilin phosphorylation and dephosphorylation in carcinoma cells. J Cell Sci. 2006;119:2871-81 pubmed
    ..Therefore, our results do not support a model for the initial activation of cofilin by dephosphorylation in response to chemoattractant stimulation in metastatic carcinoma cells. ..
  12. Mouneimne G, DesMarais V, Sidani M, Scemes E, Wang W, Song X, et al. Spatial and temporal control of cofilin activity is required for directional sensing during chemotaxis. Curr Biol. 2006;16:2193-205 pubmed
    ..These results indicate that local activation of cofilin by PLC and its global inactivation by LIMK phosphorylation combine to generate the local asymmetry of actin polymerization required for chemotaxis. ..
  13. Michelot A, Berro J, Guerin C, Boujemaa Paterski R, Staiger C, Martiel J, et al. Actin-filament stochastic dynamics mediated by ADF/cofilin. Curr Biol. 2007;17:825-33 pubmed
    ..When combined with a selection process that stabilizes filaments in bundles, this mechanism could account for the emergence and extension of actin-based structures in cells. ..
  14. Bernstein B, Bamburg J. ADF/cofilin: a functional node in cell biology. Trends Cell Biol. 2010;20:187-95 pubmed publisher
    ..We argue that this ability to respond to physiological changes by modulating those same changes makes the ADF/cofilin protein family a homeostatic regulator or 'functional node' in cell biology. ..
  15. von Blume J, Duran J, Forlanelli E, Alleaume A, Egorov M, Polishchuk R, et al. Actin remodeling by ADF/cofilin is required for cargo sorting at the trans-Golgi network. J Cell Biol. 2009;187:1055-69 pubmed publisher
    ..This type of actin-dependent compartmentalization and filtering of secretory cargo at the TGN by ADF/cofilin could explain sorting of proteins that are destined to the cell surface. ..
  16. Sun C, Magalhaes M, Glogauer M. Rac1 and Rac2 differentially regulate actin free barbed end formation downstream of the fMLP receptor. J Cell Biol. 2007;179:239-45 pubmed
  17. Meira M, Masson R, Stagljar I, Lienhard S, Maurer F, Boulay A, et al. Memo is a cofilin-interacting protein that influences PLCgamma1 and cofilin activities, and is essential for maintaining directionality during ErbB2-induced tumor-cell migration. J Cell Sci. 2009;122:787-97 pubmed publisher
    ..In summary, these data indicate that Memo also regulates actin dynamics by interacting with cofilin and enhancing its function. ..
  18. Heredia L, Helguera P, de Olmos S, Kedikian G, Sola Vigo F, LaFerla F, et al. Phosphorylation of actin-depolymerizing factor/cofilin by LIM-kinase mediates amyloid beta-induced degeneration: a potential mechanism of neuronal dystrophy in Alzheimer's disease. J Neurosci. 2006;26:6533-42 pubmed
    ..P-LIMK1-positive neurons also showed early signs of AD pathology, such as intracellular Abeta and pretangle phosphorylated tau. Thus, LIMK1 activation may play a key role in AD pathology. ..
  19. Lin M, Galletta B, Sept D, Cooper J. Overlapping and distinct functions for cofilin, coronin and Aip1 in actin dynamics in vivo. J Cell Sci. 2010;123:1329-42 pubmed publisher
    ..Together, the results suggest that all three proteins work together to promote actin disassembly, but not in a simple way, and not with equal importance. ..
  20. Daher F, Geitmann A. Actin depolymerizing factors ADF7 and ADF10 play distinct roles during pollen development and pollen tube growth. Plant Signal Behav. 2012;7:879-81 pubmed publisher
    ..The possibility to visualize both of these pollen-specific ADFs simultaneously opens avenues for future research into the regulatory function of actin binding proteins in pollen. ..
  21. Andrianantoandro E, Pollard T. Mechanism of actin filament turnover by severing and nucleation at different concentrations of ADF/cofilin. Mol Cell. 2006;24:13-23 pubmed
    ..These results establish a clear paradigm for actin turnover by cofilin in cells. ..
  22. Pavlov D, Muhlrad A, Cooper J, Wear M, Reisler E. Severing of F-actin by yeast cofilin is pH-independent. Cell Motil Cytoskeleton. 2006;63:533-42 pubmed
    ..The pH-independent severing by cofilin was confirmed using actin labeled at Cys374 with Oregon Green 488 maleimide. The depolymerization of actin by cofilin was faster at high pH. ..
  23. Garvalov B, FLYNN K, Neukirchen D, Meyn L, Teusch N, Wu X, et al. Cdc42 regulates cofilin during the establishment of neuronal polarity. J Neurosci. 2007;27:13117-29 pubmed
    ..We conclude that Cdc42 is a key regulator of axon specification, and that cofilin is a physiological downstream effector of Cdc42 in this process. ..
  24. Rust M, Gurniak C, Renner M, Vara H, Morando L, Görlich A, et al. Learning, AMPA receptor mobility and synaptic plasticity depend on n-cofilin-mediated actin dynamics. EMBO J. 2010;29:1889-902 pubmed publisher
    ..These results suggest a critical function of actin dynamics in associative learning and postsynaptic receptor availability. ..
  25. Marx N, Burgmaier M, Heinz P, Ostertag M, Hausauer A, Bach H, et al. Glucagon-like peptide-1(1-37) inhibits chemokine-induced migration of human CD4-positive lymphocytes. Cell Mol Life Sci. 2010;67:3549-55 pubmed publisher
    ..This effect provides a potential novel mechanism for how GLP-1(1-37) may modulate vascular disease. ..
  26. Chen Q, Pollard T. Actin filament severing by cofilin is more important for assembly than constriction of the cytokinetic contractile ring. J Cell Biol. 2011;195:485-98 pubmed publisher
  27. Guo J, Wang W, Yu D, Wu Y. Spinoculation triggers dynamic actin and cofilin activity that facilitates HIV-1 infection of transformed and resting CD4 T cells. J Virol. 2011;85:9824-33 pubmed publisher
    ..Our results also indicate that caution needs to be taken in data interpretation when cells are spinoculated; some of the spin-induced cellular permissiveness may be beyond the natural capacity of an infecting virus. ..
  28. Gu J, Lee C, Fan Y, Komlos D, Tang X, Sun C, et al. ADF/cofilin-mediated actin dynamics regulate AMPA receptor trafficking during synaptic plasticity. Nat Neurosci. 2010;13:1208-15 pubmed publisher
    ..These findings suggest that temporally regulated ADF/cofilin activities function in postsynaptic modifications of receptor number and spine size during synaptic plasticity. ..
  29. Stolp B, Abraham L, Rudolph J, Fackler O. Lentiviral Nef proteins utilize PAK2-mediated deregulation of cofilin as a general strategy to interfere with actin remodeling. J Virol. 2010;84:3935-48 pubmed publisher
  30. Yao J, Hennessey T, Flynt A, Lai E, Beal M, Lin M. MicroRNA-related cofilin abnormality in Alzheimer's disease. PLoS ONE. 2010;5:e15546 pubmed publisher
    ..These results suggest that microRNAs may play an important role in cytoskeletal pathology in AD. ..
  31. Kligys K, Claiborne J, DeBiase P, Hopkinson S, Wu Y, Mizuno K, et al. The slingshot family of phosphatases mediates Rac1 regulation of cofilin phosphorylation, laminin-332 organization, and motility behavior of keratinocytes. J Biol Chem. 2007;282:32520-8 pubmed
  32. Okreglak V, Drubin D. Cofilin recruitment and function during actin-mediated endocytosis dictated by actin nucleotide state. J Cell Biol. 2007;178:1251-64 pubmed
    ..These results suggest that cofilin-mediated actin filament flux is required for the multiple steps of endocytic trafficking. ..
  33. Shvetsov A, Galkin V, Orlova A, Phillips M, Bergeron S, Rubenstein P, et al. Actin hydrophobic loop 262-274 and filament nucleation and elongation. J Mol Biol. 2008;375:793-801 pubmed
    ..Our findings show an importance of the hydrophobic loop conformational dynamics in both actin nucleation and elongation and reveal that the inhibition of these two steps in the cross-linked actin can be relieved by appropriate factors. ..
  34. Minamide L, Maiti S, Boyle J, Davis R, Coppinger J, Bao Y, et al. Isolation and characterization of cytoplasmic cofilin-actin rods. J Biol Chem. 2010;285:5450-60 pubmed publisher
    ..Rod filament lengths measured by ultrastructural tomography ranged from 22 to 1480 nm. These results suggest rods form by assembly of cofilin-actin subunits, followed by self-association of ADF/cofilin-saturated F-actin. ..
  35. Bou Daher F, van Oostende C, Geitmann A. Spatial and temporal expression of actin depolymerizing factors ADF7 and ADF10 during male gametophyte development in Arabidopsis thaliana. Plant Cell Physiol. 2011;52:1177-92 pubmed publisher
    ..In the shank of elongating pollen tubes, ADF10 was associated with thick actin cables. We propose possible specific functions of these two ADFs based on their differences in expression and localization. ..
  36. Nakano K, Mabuchi I. Actin-depolymerizing protein Adf1 is required for formation and maintenance of the contractile ring during cytokinesis in fission yeast. Mol Biol Cell. 2006;17:1933-45 pubmed
    ..Tropomyosin was shown to antagonize the function of Adf1 in the contractile ring. We propose that formation and maintenance of the contractile ring are achieved by a balanced collaboration of these proteins. ..
  37. Sester U, Wabnitz G, Kirchgessner H, Samstag Y. Ras/PI3kinase/cofilin-independent activation of human CD45RA+ and CD45RO+ T cells by superagonistic CD28 stimulation. Eur J Immunol. 2007;37:2881-91 pubmed
    ..Likewise, L-plastin is not phosphorylated. Thus, superagonistic CD28 stimulation does not mimic costimulation. Instead, it leads to a Ras/PI3Kinase/cofilin-independent state of "unpolarized T cell activation". ..
  38. Wabnitz G, Nebl G, Klemke M, Schroder A, Samstag Y. Phosphatidylinositol 3-kinase functions as a Ras effector in the signaling cascade that regulates dephosphorylation of the actin-remodeling protein cofilin after costimulation of untransformed human T lymphocytes. J Immunol. 2006;176:1668-74 pubmed
    ..In addition to the insights into the regulation of cofilin, this finding discloses a to date unrecognized possibility of PI3K activation in T lymphocytes. ..
  39. Okreglak V, Drubin D. Loss of Aip1 reveals a role in maintaining the actin monomer pool and an in vivo oligomer assembly pathway. J Cell Biol. 2010;188:769-77 pubmed publisher
  40. Lee C, Han J, Bamburg J, Han L, Lynn R, Zheng J. Regulation of acetylcholine receptor clustering by ADF/cofilin-directed vesicular trafficking. Nat Neurosci. 2009;12:848-56 pubmed publisher
    ..These results suggest that spatiotemporally restricted ADF/cofilin-mediated actin dynamics regulate AChR trafficking during the development of neuromuscular synapses. ..
  41. Van Troys M, Huyck L, Leyman S, Dhaese S, Vandekerkhove J, Ampe C. Ins and outs of ADF/cofilin activity and regulation. Eur J Cell Biol. 2008;87:649-67 pubmed publisher
    ..In this framework, we describe current views on how ADF/cofilins function in migrating and invading cells. ..
  42. Goroncy A, Koshiba S, Tochio N, Tomizawa T, Sato M, Inoue M, et al. NMR solution structures of actin depolymerizing factor homology domains. Protein Sci. 2009;18:2384-92 pubmed publisher
    ..The G-actin binding site of the ADF-H domain of human HIP-55-drebrin-like protein is absent and distorted in mouse GMF beta and GMF gamma. ..
  43. Galkin V, Orlova A, Kudryashov D, Solodukhin A, Reisler E, Schröder G, et al. Remodeling of actin filaments by ADF/cofilin proteins. Proc Natl Acad Sci U S A. 2011;108:20568-72 pubmed publisher
    ..Our results show the structural plasticity of actin, suggest that other actin-binding proteins may also induce large but different conformational changes, and show that F-actin cannot be described by a single molecular model. ..
  44. Jovceva E, Larsen M, Waterfield M, Baum B, Timms J. Dynamic cofilin phosphorylation in the control of lamellipodial actin homeostasis. J Cell Sci. 2007;120:1888-97 pubmed
  45. Mohri K, Ono K, Yu R, Yamashiro S, Ono S. Enhancement of actin-depolymerizing factor/cofilin-dependent actin disassembly by actin-interacting protein 1 is required for organized actin filament assembly in the Caenorhabditis elegans body wall muscle. Mol Biol Cell. 2006;17:2190-9 pubmed
    ..These results indicate that the actin-regulating activity of AIP1 in cooperation with ADF/cofilin is essential for its in vivo function to regulate actin filament organization in muscle cells. ..
  46. Tammana T, Sahasrabuddhe A, Mitra K, Bajpai V, Gupta C. Actin-depolymerizing factor, ADF/cofilin, is essentially required in assembly of Leishmania flagellum. Mol Microbiol. 2008;70:837-52 pubmed publisher
    ..These results for the first time indicate that the actin dynamics-regulating protein ADF/cofilin plays a critical role in assembly and motility of the eukaryotic flagellum...
  47. Bamburg J, Bernstein B. ADF/cofilin. Curr Biol. 2008;18:R273-5 pubmed publisher
  48. Fernández B, Gaspar P, Bras Pereira C, Jezowska B, Rebelo S, Janody F. Actin-Capping Protein and the Hippo pathway regulate F-actin and tissue growth in Drosophila. Development. 2011;138:2337-46 pubmed publisher
    ..Taken together, these findings indicate a novel interplay between Hippo pathway activity and actin filament dynamics that is essential for normal growth control. ..
  49. Vogel S, Wottawa M, Farhat K, Zieseniss A, Schnelle M, Le Huu S, et al. Prolyl hydroxylase domain (PHD) 2 affects cell migration and F-actin formation via RhoA/rho-associated kinase-dependent cofilin phosphorylation. J Biol Chem. 2010;285:33756-63 pubmed publisher
    ..Because cofilin phosphorylation impairs its actin-severing function, this may explain the F-actin phenotype, thereby providing a functional link between PHD2-dependent signaling and cell motility. ..
  50. Oser M, Yamaguchi H, Mader C, Bravo Cordero J, Arias M, Chen X, et al. Cortactin regulates cofilin and N-WASp activities to control the stages of invadopodium assembly and maturation. J Cell Biol. 2009;186:571-87 pubmed publisher
  51. Shi Y, Pontrello C, DeFea K, Reichardt L, Ethell I. Focal adhesion kinase acts downstream of EphB receptors to maintain mature dendritic spines by regulating cofilin activity. J Neurosci. 2009;29:8129-42 pubmed publisher
  52. Breitsprecher D, Koestler S, Chizhov I, Nemethova M, Mueller J, Goode B, et al. Cofilin cooperates with fascin to disassemble filopodial actin filaments. J Cell Sci. 2011;124:3305-18 pubmed publisher
    ..These results identify a new mechanism of filopodium disassembly involving both fascin and cofilin. ..
  53. Goyal P, Pandey D, Br nnert D, Hammer E, Zygmunt M, Siess W. Cofilin oligomer formation occurs in vivo and is regulated by cofilin phosphorylation. PLoS ONE. 2013;8:e71769 pubmed publisher
    ..Cofilin oligomerization might explain the dual action of cofilin on actin dynamics in vivo...