• Cofilin is a widely distributed intracellular actin-modulating protein that binds and depolymerizes filamentous F-actin and inhibits the polymerization of monomeric G-actin in a pH-dependent manner. (wikipedia.org)
  • Cofilin binds to F-actin and exhibits pH-sensitive F-actin depolymerizing activity. (thermofisher.com)
  • Our results showing that only dephosphorylated (activated) cofilin binds with F-actin support previous observations that the state of cofilin phosphorylation determines its association with F-actin. (uni-muenchen.de)
  • We identified for the first time that cofilin binds to microtubules at the expense of tau - essentially kicking tau off the microtubules and interfering with tau-induced microtubule assembly. (usf.edu)
  • Upon release, we find that cofilin binds to and severs F-actin, which is coincident with actin polymerization and lamellipod formation. (rupress.org)
  • Cofilin binds preferentially to ADP-actin subunits within actin filaments. (rupress.org)
  • We propose that ADF/cofilin-dependent severing of actin filaments exposes and promotes the activation of SPCA1, which pumps Ca(2+) into the lumen of the TGN for the sorting of the class of secretory cargo that binds Ca(2+). (upf.edu)
  • Only dephosphorylated cofilin binds to G-actin and translocates to mitochondria during AITC-mediated apoptosis. (tech-strategy.org)
  • Conclusions These findings support a model in which induction of apoptosis by AITC stems primarily from activation of ROCK1 and PTEN and inactivation of PI3K leading in turn to activation of PP1 and PP2A resulting in dephosphorylation of cofilin which binds to G-actin and translocates Fmoc-Lys(Me3)-OH chloride to mitochondria culminating in the dysfunction of mitochondria release of cytochrome c and apoptosis. (tech-strategy.org)
  • One group reports that reelin signaling leads to serine3-phosphorylation of cofilin-1, and this interaction may play a role in the reelin-related regulation of neuronal migration. (wikipedia.org)
  • The signaling pathway Rho-kinase/LIMKs/cofilin phosphorylation during platelet activation and the question, how the phosphorylation of cofilin affects the actin dynamics underlying platelet activation, has not previously been studied. (uni-muenchen.de)
  • Activation of cofilin kinases, LIMK1 or LIMK2, leads to phosphorylation of cofilin at serine 3. (ecmbio.com)
  • n-cofilin), also known as CFL1, is a human gene, part of the ADF/cofilin family. (wikipedia.org)
  • The EPHB2-FAK pathway partially promotes dendritic spine stability through LIMK-mediated cofilin (CFL1) phosphorylation (Shi et al. (reactome.org)
  • Rho-kinase regulates a second pathway that involves activation of LIM-kinases (LIMKs) and subsequent phosphorylation and inactivation of cofilin, an actin dynamizing protein. (uni-muenchen.de)
  • ADF)/cofilin family which regulates actin dynamics. (tech-strategy.org)
  • It is involved in the translocation of actin-cofilin complex from cytoplasm to nucleus. (wikipedia.org)
  • Recent studies reported a mitochondrial translocation of n-cofilin during apoptosis. (nature.com)
  • 8 Recently, it was shown that n-cofilin translocates to mitochondria during the early phase of apoptosis, but the mechanism for this translocation remained obscure. (nature.com)
  • Mechanistic study revealed that interruption of ROCK1/PTEN/PI3K signaling pathway plays a critical role in AITC-mediated dephosphorylation and mitochondrial translocation of cofilin and apoptosis. (tech-strategy.org)
  • In 1994 we demonstrated for the TRV130 HCl (Oliceridine) very first time that cofilin translocation in to the nucleus succeeds triggering of the cell surface area receptor namely Compact disc2 excitement of untransformed human being T cells 37. (ap26113.com)
  • of cofilin on serine 3 must enable its nuclear translocation 35. (ap26113.com)
  • Cofilin consists of a nuclear localization series (KKRKK) like the nuclear translocation sign series of simian disease 40T antigen 68-69 (or in petri meals covered with integrin-ligands data and data produced from T cells or additional cellular systems. (ap26113.com)
  • The study builds upon previous work at USF Health showing that Aβ activates cofilin through a protein known as Slingshot, or SSH1. (usf.edu)
  • Cofilin activity is regulated by its phosphorylation status, and is negatively regulated by serine/threonine kinases, LIM kinases, and testis-specific protein kinase via phosphorylation at Ser-3 [ 6 - 8 ]. (oncotarget.com)
  • Phospho-cofilin is dephosphorylated and reactivated by Slingshot (SSH), a member of the conserved family of protein phosphatases [ 9 - 10 ]. (oncotarget.com)
  • For control lysate, the recombinant Cofilin 1 protein was exposed to buffer only (Cat. (ecmbio.com)
  • Cofilin can be an actin-binding protein that depolymerizes and/or TRV130 HCl (Oliceridine) severs actin filaments. (ap26113.com)
  • He explains that some of these studies use transgenic zebrafish that over-express a protein called Cofilin which is known to play an important role in the formation and modification of connections in the brain. (coherent.com)
  • Dephosphorylation and activation of cofilin lead to severing and depolymerization of existing actin filaments. (uni-muenchen.de)
  • Inhibition of the Rho-kinase/LIMK-1 pathway unmasked cofilin dephosphorylation suggesting that during shape change the simultaneous activation of a cofilin phosphatase counteracts the effect of LIMK-1 for phosphorylating cofilin. (uni-muenchen.de)
  • Furthermore, the results clearly showed that cofilin dephosphorylation is also independent and upstream of secretion, since the onset of cofilin dephosphorylation was as rapid as secretion in thrombin-stimulated platelets and also occurred in the absence of dense granule secretion in LPA (10 µM)-stimulated platelets. (uni-muenchen.de)
  • Since the kinetics of cofilin phospho-cycle was similar during secretion and platelet aggregation in LPA- and thrombin-stimulated cells, I propose a general two-step regulatory process for cofilin phospho-cycle underlying primarily secretion, and subsequently platelet aggregation: dephosphorylation by a cofilin phosphatase and then rephosphorylation by the Rho-kinase/LIMK-1 pathway. (uni-muenchen.de)
  • Our study also showed that AITC-mediated inhibition of tumor growth of mouse leukemia xenograft model is usually in association with dephosphorylation of cofilin. (tech-strategy.org)
  • and in several tumor xenograft models results indicate that dephosphorylation of cofilin may contribute to AITC-mediated inhibitory effects on tumor growth of U937 Fmoc-Lys(Me3)-OH chloride xenograft mouse model. (tech-strategy.org)
  • transmission 1) together with accessory receptors (transmission 2) or triggering through the chemokine SDF1α (stromal cell-derived element 1α) induce Ras-dependent dephosphorylation of cofilin which is important for immune synapse formation T-cell activation and T-cell migration. (ap26113.com)
  • This phosphorylation disrupts cofilin binding to actin in vitro and in vivo. (ecmbio.com)
  • The following product was used in this experiment: Cofilin Polyclonal Antibody from Thermo Fisher Scientific, catalog # 10960-1-AP. (thermofisher.com)
  • A major modulator of actin filament disassembly is the actin-depolymerization factor/cofilin family of proteins (hereafter referred to as cofilin). (rupress.org)
  • Cofilin stimulates actin depolymerization and severance of actin filaments at the protruding ends, thereby promoting their rapid turnover and determining the direction of cell movement [ 4 - 5 ]. (oncotarget.com)
  • The dual function of cofilin namely depolymerization and severing makes it a key molecule controlling actin dynamics. (ap26113.com)
  • human liver tissue were subjected to SDS PAGE followed by western blot with 11848-1-AP (Cofilin 2 antibody) at dilution of 1:400 incubated at room temperature for 1.5 hours. (ptglab.com)
  • Immunohistochemical analysis of paraffin-embedded human skeletal muscle tissue slide using 11848-1-AP (Cofilin 2 antibody at dilution of 1:50 (under 10x lens). (ptglab.com)
  • Non-muscle cofilin (n-cofilin) is a member of the ADF/cofilin family of actin depolymerizing proteins. (nature.com)
  • Importantly, the mitochondrial association of n-cofilin and ADF had no impact on apoptosis signaling because ablation of either n-cofilin, ADF, or both proteins together did not change cell death progression. (nature.com)
  • Members of the ADF/cofilin (AC) family are actin-severing proteins that regulate actin remodeling during cell migration, cytokinesis, axon development, and immune cell activation. (ecmbio.com)
  • Actin-severing proteins ADF/cofilin are required for the sorting of secretory cargo at the trans-Golgi network (TGN) in mammalian cells. (upf.edu)
  • As these studies also revealed impaired cytochrome c release and a block in apoptosis upon small interfering RNA-mediated n-cofilin knockdown, n-cofilin was postulated to be essential for apoptosis induction. (nature.com)
  • To elucidate the general importance of ADF/cofilin activity for apoptosis, we exposed mouse embryonic fibroblasts deficient for n-cofilin, ADF (actin depolymerizing factor), or all ADF/cofilin isoforms to well-characterized apoptosis inducers. (nature.com)
  • Thus, we conclude that ADF/cofilin activity is not generally required for induction or progression of apoptosis in mammalian cells. (nature.com)
  • Interestingly, mitochondrial association of ADF and n-cofilin during apoptosis was preceded by, and dependent on, actin that translocated by a yet unknown mechanism to mitochondria during cell death. (nature.com)
  • To test the relevance of ADF/cofilin activity for apoptotic processes, we here employed a genetically well-defined system of mouse embryonic fibroblasts (MEFs) devoid of any ADF/cofilin activity and challenged these cells with well-characterized apoptosis inducers. (nature.com)
  • We found that, upon induction of apoptosis in control MEFs, n-cofilin, and its homolog ADF translocated to mitochondria together with actin. (nature.com)
  • In summary, our work demonstrates that in mammalian cells ADF/cofilin activity is not generally required for efficient induction of apoptosis. (nature.com)
  • Here, we provide the first in vivo data that directly visualize the spatial and temporal regulation of cofilin by PIP 2 in living cells. (rupress.org)
  • Both extrinsic factors of the microenvironment and intrinsic signal transduction events mediate this cofilin orchestration through phospho- phospholipid and redox regulation of cofilin within human T cells (look at from the bull's-eye formed organization from the SMACs in the T-cell membrane. (ap26113.com)
  • NMR Study of the Molecular Basis for Phosphoinositide Regulation of the Cofilin-Actin Interactions. (cathdb.info)
  • We show that EGF induces a rapid loss of PIP 2 through PLC activity, resulting in a release and activation of a membrane-bound pool of cofilin. (rupress.org)
  • The membrane-bound small fraction of cofilin can be dephosphorylated but held inactive by binding to PI(4 5 Both cytoplasmic fraction with least a percentage from the membrane-bound cofilin are turned on by T-cell costimulation. (ap26113.com)
  • Membrane-bound dephosphorylated cofilin could be triggered by PLC-dependent PI(4 5 cleavage releasing dephosphorylated cofilin into the cytoplasm 38 40 Thereby the cytoplasmic pool of activated cofilin is increased and actin dynamics are reinforced. (ap26113.com)
  • Cofilin localizes towards the … TRV130 HCl (Oliceridine) Nuclear features of cofilin Furthermore to its function in the cytoplasm dephosphorylated cofilin has the capacity to translocate in to the nucleus. (ap26113.com)
  • Moreover dephosphorylated cofilin can translocate into the nucleus 37 where it may act as actin shuttle and as chaperone for RNA polymerase II-dependent gene transcription 70-141. (ap26113.com)
  • 5 Actin dynamics critically depend on members of the ADF/cofilin family that comprises muscle cofilin (m-cofilin), non-muscle cofilin (n-cofilin), and ADF (actin depolymerizing factor). (nature.com)
  • Using a mouse model for early-stage tauopathy, Dr. Kang and his colleagues showed that Aβ-activated cofilin promotes tauopathy by displacing the tau molecules directly binding to microtubules, destabilizes microtubule dynamics, and disrupts synaptic function (neuron signaling) - all key factors in Alzheimer's disease progression. (usf.edu)
  • In this study, we analyzed the dynamics of fluorescently tagged cofilin and the role of cofilin-mediated actin turnover during endocytosis in Saccharomyces cerevisiae . (rupress.org)
  • Cofilin and its role in actin dynamics have been studied extensively in vitro. (rupress.org)
  • In contrast in a reducing environment even phosphatidylinositol 4 5 -bound cofilin becomes active leading to actin dynamics in the vicinity of the plasma membrane. (ap26113.com)
  • For preparation of Ser-3 phosphorylated Cofilin, purified human Cofilin 1 was phosphorylated in vitro with His-tagged mouse recombinant LIM Kinase 1 for 30 min. (ecmbio.com)
  • These observations led to the hypothesis that cofilin localization is largely dependent on accessory factors or other regulatory inputs, such as phosphorylation or pH. (rupress.org)
  • Interestingly, our data suggest no direct interaction of n-cofilin and ADF with mitochondria, but a rather indirect, actin-mediated association. (nature.com)
  • However, the molecular mechanism of cofilin recruitment to actin networks during dynamic actin-mediated processes in living cells and cofilin's precise in vivo functions have not been determined. (rupress.org)
  • After stimulation with LPA and thrombin under conditions, where platelet aggregation could not occur, the kinetics of cofilin de- and rephosphorylation were unperturbed indicating their independence of integrin IIbβ3 engagement. (uni-muenchen.de)
  • The researchers also demonstrated that genetically reducing cofilin helped prevent the tau aggregation leading to Alzheimer's-like brain damage in mice. (usf.edu)
  • While investigating the molecular relationship between amyloid and tau, University of South Florida neuroscientists discovered that the Aβ-activated enzyme cofilin plays an essential intermediary role in worsening tau pathology. (usf.edu)
  • Genetic and biochemical analysis of a conditional allele of cofilin showed that the actin filament disassembly activity of cofilin is essential for fluid-phase endocytosis ( Lappalainen and Drubin, 1997 ). (rupress.org)
  • Therefore it is not surprising that cofilin expression is essential for cell survival. (ap26113.com)
  • Due to this essential role cofilin needs to be tightly controlled. (ap26113.com)
  • Slingshot (SSH) is a member of the conserved family of cofilin phosphatases that plays a critical role in cell membrane protrusion and migration by transforming inactive phosphorylated cofilin to an active form. (oncotarget.com)
  • Surprisingly, the activation of LIMK-1 failed to increase cofilin phosphorylation during shape change induced by LPA as well as by thrombin. (uni-muenchen.de)
  • In addition to the well-established three signals for T-cell activation this microenvironmental control of cofilin delivers a modulating signal for T-cell-dependent immune reactions. (ap26113.com)
  • Cytoplasmic cofilin becomes dephosphorylated through costimulation-induced activation of Ras and its own downstream effectors MEK and PI3K 51. (ap26113.com)
  • Accordingly, SSH-1L/cofilin signaling played a critical role in primary breast cancer metastasis and was a potential therapeutic target for breast cancer treatment. (oncotarget.com)
  • In mammals, there are three members of the AC family, muscle-specific cofilin (cofilin 2), non-muscle cofilin (cofilin 1), and ADF. (ecmbio.com)
  • Primarily cofilin was recognized in intranuclear actin TRV130 HCl (Oliceridine) rods pursuing treatment of the mouse fibroblast cell range C3H-ZK with dimethylsulfoxide or pursuing exposure of the cells to temperature shock 67. (ap26113.com)
  • Whether cofilin activity results in F-actin shrinking or enhanced polymerization depends on the conditions and availability of G-actin in the specific area within the cell 39 40 and is likely influenced by different signaling cascades. (ap26113.com)
  • In resting human being T cells cofilin is definitely inactive and exists in specific subcellular locations mainly. (ap26113.com)
  • Cytoplasmic cofilin is definitely phosphorylated and therefore within an inactive state mainly. (ap26113.com)
  • In living cells, cofilin is not necessary for actin assembly on endocytic membranes but is recruited to molecularly aged adenosine diphosphate actin filaments and is necessary for their rapid disassembly. (rupress.org)
  • Figure 4 Spatio-temporal and microenvironmental control of cofilin in T cells. (ap26113.com)
  • Cofilin is the major mediator of actin filament turnover in vivo. (rupress.org)
  • Defects in cofilin function alter the morphology of actin networks in vivo and reduce the rate of actin flux through actin networks. (rupress.org)
  • The molecular determinants of cofilin recruitment to actin filaments in vivo have not been fully investigated. (rupress.org)
  • These results suggest that cofilin-mediated actin filament flux is required for the multiple steps of endocytic trafficking. (rupress.org)
  • The function of SSH-1L was evaluated by gene knockdown and quantitative real-time polymerase chain reaction detection of cofilin expression in MDA-MB-231, MCF-7, and SK-BR-3 human breast cancer cell lines. (oncotarget.com)
  • Cofilin 1 Control Lysate is supplied at a concentration of 10 ng/µl in electrophoresis sample buffer (62.5 mM Tris pH 6.8, 2% SDS, 5% glycerol, 0.003% bromophenol blue, 0.9% β-mercaptoethanol). (ecmbio.com)
  • Loss of SSH-1L expression decreased the nonphosphorylated, active form of cofilin in SK-BR-3 and MDA-MB-231 cell lines, which was associated with reduced cell motility. (oncotarget.com)
  • An amyloid plaque (stained red), one of the two major brain lesions of Alzheimer's disease, is shown here with the Aβ-activated enzyme cofilin (green) and nerve cell nuclei (blue). (usf.edu)
  • Cofilin is TRV130 HCl (Oliceridine) inactivated by oxidation provoking T-cell hyporesponsiveness or necrotic-like programmed cell death. (ap26113.com)
  • Cofilin 1 has been shown to interact with HSPH1 and LIMK1. (wikipedia.org)
  • ADF/Cofilin-Mediated Actin Retrograde Flow Directs Neurite Formation in the Developing Brain. (mpg.de)
  • In humans, cofilin 1 and ADF have 72% identity, with the major amino acid differences found in the C-terminal region. (ecmbio.com)