Actin Capping Protein

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John A. Cooper - One of the best experts on this subject based on the ideXlab platform.

  • comparative analysis of cpi motif regulation of biochemical functions of Actin Capping Protein
    Biochemistry, 2020
    Co-Authors: Patrick Mcconnell, Marlene Mekel, Alexander G Kozlov, Olivia L Mooren, Timothy M Lohman, John A. Cooper
    Abstract:

    The heterodimeric Actin Capping Protein (CP) is regulated by a set of Proteins that contain CP-interActing (CPI) motifs. Outside of the CPI motif, the sequences of these Proteins are unrelated and ...

  • comparative analysis of cpi motif regulation of biochemical functions of Actin Capping Protein
    bioRxiv, 2020
    Co-Authors: Patrick Mcconnell, Marlene Mekel, Alexander G Kozlov, Olivia L Mooren, Timothy M Lohman, John A. Cooper
    Abstract:

    The heterodimeric Actin Capping Protein (CP) is regulated by a set of Proteins that contain CP-interActing (CPI) motifs. Outside of the CPI motif, the sequences of these Proteins are unrelated and distinct. The CPI motif and surrounding sequences are conserved within a given Protein family, when compared to those of other CPI-motif Protein families. Using biochemical assays with purified Proteins, we compared the ability of CPI-motif-containing peptides from different Protein families to a) bind to CP, b) allosterically inhibit barbed-end Capping by CP, and c) allosterically inhibit interaction of CP with V-1, another regulator of CP. We found large differences in potency among the different CPI-motif-containing peptides, and the different functional assays showed different orders of potency. These biochemical differences among the CPI-motif peptides presumably reflect interactions between CP and CPI-motif peptides involving amino-acid residues that are conserved but are not part of the strictly defined consensus, as it was originally identified in comparisons of sequences of CPI motifs(1, 2) across all Protein families (1, 2). These biochemical differences may be important for conserved distinct functions of CPI-motif Protein families in cells with respect to the regulation of CP activity and Actin assembly near membranes.

  • mechanism for carmil Protein inhibition of heterodimeric Actin Capping Protein
    Journal of Biological Chemistry, 2012
    Co-Authors: Taekyung Kim, David Sept, Geoffrey E Ravilious, John A. Cooper
    Abstract:

    Capping Protein (CP) controls the polymerization of Actin filaments by Capping their barbed ends. In lamellipodia, CP dissociates from the Actin cytoskeleton rapidly, suggesting the possible existence of an unCapping factor, for which the Protein CARMIL (Capping Protein, Arp2/3 and myosin-I linker) is a candidate. CARMIL binds to CP via two motifs. One, the CP interaction (CPI) motif, is found in a number of unrelated Proteins; the other motif is unique to CARMILs, the CARMIL-specific interaction motif. A 115-aa CARMIL fragment of CARMIL with both motifs, termed the CP-binding region (CBR), binds to CP with high affinity, inhibits Capping, and causes unCapping. We wanted to understand the structural basis for this function. We used a collection of mutants affecting the Actin-binding surface of CP to test the possibility of a steric-blocking model, which remained open because a region of CBR was not resolved in the CBR/CP co-crystal structure. The CP Actin-binding mutants bound CBR normally. In addition, a CBR mutant with all residues of the unresolved region changed showed nearly normal binding to CP. Having ruled out a steric blocking model, we tested an allosteric model with molecular dynamics. We found that CBR binding induces changes in the conformation of the Actin-binding surface of CP. In addition, ∼30-aa truncations on the Actin-binding surface of CP decreased the affinity of CBR for CP. Thus, CARMIL promotes unCapping by binding to a freely accessible site on CP bound to a filament barbed end and inducing a change in the conformation of the Actin-binding surface of CP.

  • New Insights into Mechanism and Regulation of Actin Capping Protein
    International review of cell and molecular biology, 2008
    Co-Authors: John A. Cooper, David Sept
    Abstract:

    The heterodimeric Actin Capping Protein, referred to here as “CP,” is an essential element of the Actin cytoskeleton, binding to the barbed ends of Actin filaments and regulating their polymerization. In vitro, CP has a critical role in the dendritic nucleation process of Actin assembly mediated by Arp2/3 complex, and in vivo, CP is important for Actin assembly and Actin-based process of morphogenesis and differentiation. Recent studies have provided new insight into the mechanism of CP binding the barbed end, which raises new possibilities for the dynamics of CP and Actin in cells. In addition, a number of molecules that bind and regulate CP have been discovered, suggesting new ideas for how CP may integrate into diverse processes of cell physiology.

  • structure function analysis of the interaction of phosphatidylinositol 4 5 bisphosphate with Actin Capping Protein implications for how Capping Protein binds the Actin filament
    Journal of Biological Chemistry, 2007
    Co-Authors: Kyoungtae Kim, David Sept, Michelle E. Mccully, Nandini Bhattacharya, Boyd Butler, John A. Cooper
    Abstract:

    The heterodimeric Actin-Capping Protein (CP) can be inhibited by polyphosphoinositides, which may be important for Actin polymerization at membranes in cells. Here, we have identified a conserved set of basic residues on the surface of CP that are important for the interaction with phosphatidylinositol 4,5-bisphosphate (PIP2). Computational docking studies predicted the identity of residues involved in this interaction, and functional and physical assays with site-directed mutants of CP confirmed the prediction. The PIP2 binding site overlaps with the more important of the two known Actin-binding sites of CP. Correspondingly, we observed that loss of PIP2 binding correlated with loss of Actin binding among the mutants. Using TIRF (total internal reflection fluorescence) microscopy, we observed that PIP2 rapidly converted capped Actin filaments to a growing state, consistent with unCapping. Together, these results extend our understanding of how CP binds to the barbed end of the Actin filament, and they support the idea that CP can “wobble” when bound to the barbed end solely by the C-terminal “tentacle” of its β-subunit.

Jeffrey S. Simske - One of the best experts on this subject based on the ideXlab platform.

  • the minus end Actin Capping Protein unc 94 tropomodulin regulates development of the caenorhabditis elegans intestine
    Developmental Dynamics, 2014
    Co-Authors: Elisabeth Coxpaulson, Vincent L. Cannataro, Thomas Gallagher, Corey M. Hoffman, Gary Mantione, Matthew Mcintosh, Malan Silva, Nicole Vissichelli, Rachel Walker, Jeffrey S. Simske
    Abstract:

    Background: Tropomodulins are Actin-Capping Proteins that regulate the stability of the slow-growing, minus-ends of Actin filaments. The C. elegans tropomodulin homolog, UNC-94, has sequence and functional similarity to vertebrate tropomodulins. We investigated the role of UNC-94 in C. elegans intestinal morphogenesis. Results: In the embryonic C. elegans intestine, UNC-94 localizes to the terminal web, an Actin- and intermediate filament-rich structure that underlies the apical membrane. Loss of UNC-94 function results in areas of flattened intestinal lumen. In worms homozygous for the strong loss-of-function allele, unc-94(tm724), the terminal web is thinner and the amount of F-Actin is reduced, pointing to a role for UNC-94 in regulating the structure of the terminal web. The non-muscle myosin, NMY-1, also localizes to the terminal web, and we present evidence that increasing actomyosin contractility by depleting the myosin phosphatase regulatory subunit, mel-11, can rescue the flattened lumen phenotype of unc-94 mutants. Conclusions: The data support a model in which minus-end Actin Capping by UNC-94 promotes proper F-Actin structure and contraction in the terminal web, yielding proper shape of the intestinal lumen. This establishes a new role for a tropomodulin in regulating lumen shape during tubulogenesis. Developmental Dynamics 243:753–764, 2014. V C 2014 Wiley Periodicals, Inc.

  • The Minus-End Actin Capping Protein, UNC-94/Tropomodulin, Regulates Development of the Caenorhabditis elegans Intestine
    Developmental Dynamics, 2014
    Co-Authors: Elisabeth Cox-paulson, Vincent L. Cannataro, Thomas Gallagher, Corey M. Hoffman, Gary Mantione, Matthew Mcintosh, Malan Silva, Nicole Vissichelli, Rachel L. Walker, Jeffrey S. Simske
    Abstract:

    Background: Tropomodulins are Actin-Capping Proteins that regulate the stability of the slow-growing, minus-ends of Actin filaments. The C. elegans tropomodulin homolog, UNC-94, has sequence and functional similarity to vertebrate tropomodulins. We investigated the role of UNC-94 in C. elegans intestinal morphogenesis. Results: In the embryonic C. elegans intestine, UNC-94 localizes to the terminal web, an Actin- and intermediate filament-rich structure that underlies the apical membrane. Loss of UNC-94 function results in areas of flattened intestinal lumen. In worms homozygous for the strong loss-of-function allele, unc-94(tm724), the terminal web is thinner and the amount of F-Actin is reduced, pointing to a role for UNC-94 in regulating the structure of the terminal web. The non-muscle myosin, NMY-1, also localizes to the terminal web, and we present evidence that increasing actomyosin contractility by depleting the myosin phosphatase regulatory subunit, mel-11, can rescue the flattened lumen phenotype of unc-94 mutants. Conclusions: The data support a model in which minus-end Actin Capping by UNC-94 promotes proper F-Actin structure and contraction in the terminal web, yielding proper shape of the intestinal lumen. This establishes a new role for a tropomodulin in regulating lumen shape during tubulogenesis. Developmental Dynamics 243:753–764, 2014. V C 2014 Wiley Periodicals, Inc.

Sofia Khaitlina - One of the best experts on this subject based on the ideXlab platform.

  • 1 REGULATION OF SODIUM CHANNEL ACTIVITY BY Capping OF Actin FILAMENTS
    2013
    Co-Authors: Ekaterina Shumilina, Yuri A. Negulyaev, Elena A. Morachevskaya, Sofia Khaitlina
    Abstract:

    cell. 2 Ion transport in various tissues can be regulated by the cortical Actin cytoskeleton. Specifically, involvement of Actin dynamics in the regulation of non-voltage-gated sodium channels has been shown. Here, inside-out patch clamp experiments were performed to study the effect of the heterodimeric Actin Capping Protein CapZ on sodium channel regulation in leukemia K562 cells. The channels were activated by cytochalasininduced disruption of Actin filaments and inactivated by G-Actin under ionic conditions promoting rapid Actin polymerization. CapZ had no direct effect on channel activity. However, being added together with G-Actin, CapZ prevented Actin-induced channel inactivation, and this effect occurred at CapZ/Actin molar ratios from 1:5 to 1:100. When Actin was allowed to polymerize at the plasma membrane to induce partial channel inactivation, subsequent addition of CapZ restored the channel activity. These results can be explained by CapZ-induced inhibition of further assembly of Actin filaments at the plasma membrane due to the modification of Actin dynamics by CapZ. No effect on the channel activity was observed in response to F-Actin confirming that the mechanism of channel inactivation does not involve interaction of the channel with preformed filaments. Our data show that Actin-Capping Protein can participate in the cytoskeletonassociated regulation of sodium transport in nonexcitable cells

  • Regulation of Sodium Channel Activity by Capping of Actin Filaments
    Molecular biology of the cell, 2003
    Co-Authors: Ekaterina Shumilina, Yuri A. Negulyaev, Elena A. Morachevskaya, Horst Hinssen, Sofia Khaitlina
    Abstract:

    Ion transport in various tissues can be regulated by the cortical Actin cytoskeleton. Specifically, involvement of Actin dynamics in the regulation of nonvoltage-gated sodium channels has been shown. Herein, inside-out patch clamp experiments were performed to study the effect of the heterodimeric Actin Capping Protein CapZ on sodium channel regulation in leukemia K562 cells. The channels were activated by cytochalasin-induced disruption of Actin filaments and inactivated by G-Actin under ionic conditions promoting rapid Actin polymerization. CapZ had no direct effect on channel activity. However, being added together with G-Actin, CapZ prevented Actin-induced channel inactivation, and this effect occurred at CapZ/Actin molar ratios from 1:5 to 1:100. When Actin was allowed to polymerize at the plasma membrane to induce partial channel inactivation, subsequent addition of CapZ restored the channel activity. These results can be explained by CapZ-induced inhibition of further assembly of Actin filaments at the plasma membrane due to the modification of Actin dynamics by CapZ. No effect on the channel activity was observed in response to F-Actin, confirming that the mechanism of channel inactivation does not involve interaction of the channel with preformed filaments. Our data show that Actin-Capping Protein can participate in the cytoskeleton-associated regulation of sodium transport in nonexcitable cells.

  • Regulation of sodium channel activity by Capping of Actin filaments
    'American Society for Cell Biology (ASCB)', 2003
    Co-Authors: Ekaterina Shumilina, Yuri A. Negulyaev, Elena A. Morachevskaya, Hinssen Horst, Sofia Khaitlina
    Abstract:

    Shumilina EV, Negulyaev YA, Morachevskaya EA, Hinssen H, Khaitlina SY. Regulation of sodium channel activity by Capping of Actin filaments. MOLECULAR BIOLOGY OF THE CELL. 2003;14(4):1709-1716.Ion transport in various tissues can be regulated by the cortical Actin cytoskeleton. Specifically, involvement of Actin dynamics in the regulation of nonvoltage-gated sodium channels has been shown. Herein, inside-out patch clamp experiments were performed to study the effect of the heterodimeric Actin Capping Protein CapZ on sodium channel regulation in leukemia K562 cells. The channels were activated by cytochalasin-induced disruption of Actin filaments and inactivated by G-Actin under ionic conditions promoting rapid Actin polymerization. CapZ had no direct effect on channel activity. However, being added together with G-Actin, CapZ prevented Actin-induced channel inactivation, and this effect occurred at CapZ/Actin molar ratios from 1:5 to 1:100. When Actin was allowed to polymerize at the plasma membrane to induce partial channel inactivation, subsequent addition of CapZ restored the channel activity. These results can be explained by CapZ-induced inhibition of further assembly of Actin filaments at the plasma membrane due to the modification of Actin dynamics by CapZ. No effect on the channel activity was observed in response to F-Actin, confirming that the mechanism of channel inactivation does not involve interaction of the channel with preformed filaments. Our data show that Actin-Capping Protein can participate in the cytoskeleton-associated regulation of sodium transport in nonexcitable cells

Maki K. Yamada - One of the best experts on this subject based on the ideXlab platform.

  • Activity‐dependent localization in spines of the F‐Actin Capping Protein CapZ screened in a rat model of dementia
    Genes to cells : devoted to molecular & cellular mechanisms, 2010
    Co-Authors: Takuma Kitanishi, Jun Sakai, Shinichi Kojima, Yoshito Saitoh, Kaoru Inokuchi, Masahiro Fukaya, Masahiko Watanabe, Norio Matsuki, Maki K. Yamada
    Abstract:

    Actin reorganization in dendritic spines is hypothesized to underlie neuronal plasticity. Actin-related Proteins, therefore, might serve as useful markers of plastic changes in dendritic spines. Here, we utilized memory deficits induced by fimbria-fornix transection (FFT) in rats as a dementia model to screen candidate memory-associated molecules by using a two-dimensional gel method. Comparison of Protein profiles between the transected and control sides of hippocampi after unilateral FFT revealed a reduction in the F-Actin Capping Protein (CapZ) signal on the FFT side. Subsequent immunostaining of brain sections and cultured hippocampal neurons revealed that CapZ localized in dendritic spines and the signal intensity in each spine varied widely. The CapZ content decreased after suppression of neuronal firing by tetrodotoxin treatment in cultured neurons, indicating rapid and activity-dependent regulation of CapZ accumulation in spines. To test input specificity of CapZ accumulation in vivo, we delivered high-frequency stimuli to the medial perforant path unilaterally in awake rats. This path selectively inputs to the middle molecular layer of the dentate gyrus, where CapZ immunoreactivity increased. We conclude that activity-dependent, synapse-specific regulation of CapZ redistribution might be important in both maintenance and remodeling of synaptic connections in neurons receiving specific spatial and temporal patterns of inputs.

  • activity dependent localization in spines of the f Actin Capping Protein capz screened in a rat model of dementia
    Genes to Cells, 2010
    Co-Authors: Takuma Kitanishi, Jun Sakai, Shinichi Kojima, Yoshito Saitoh, Kaoru Inokuchi, Masahiro Fukaya, Masahiko Watanabe, Norio Matsuki, Maki K. Yamada
    Abstract:

    Actin reorganization in dendritic spines is hypothesized to underlie neuronal plasticity. Actin-related Proteins, therefore, might serve as useful markers of plastic changes in dendritic spines. Here, we utilized memory deficits induced by fimbria-fornix transection (FFT) in rats as a dementia model to screen candidate memory-associated molecules by using a two-dimensional gel method. Comparison of Protein profiles between the transected and control sides of hippocampi after unilateral FFT revealed a reduction in the F-Actin Capping Protein (CapZ) signal on the FFT side. Subsequent immunostaining of brain sections and cultured hippocampal neurons revealed that CapZ localized in dendritic spines and the signal intensity in each spine varied widely. The CapZ content decreased after suppression of neuronal firing by tetrodotoxin treatment in cultured neurons, indicating rapid and activity-dependent regulation of CapZ accumulation in spines. To test input specificity of CapZ accumulation in vivo, we delivered high-frequency stimuli to the medial perforant path unilaterally in awake rats. This path selectively inputs to the middle molecular layer of the dentate gyrus, where CapZ immunoreactivity increased. We conclude that activity-dependent, synapse-specific regulation of CapZ redistribution might be important in both maintenance and remodeling of synaptic connections in neurons receiving specific spatial and temporal patterns of inputs.

Andrés F Muro - One of the best experts on this subject based on the ideXlab platform.

  • The erythrocyte skeletons of beta-adducin deficient mice have altered levels of tropomyosin, tropomodulin and EcapZ.
    FEBS Letters, 2004
    Co-Authors: Fabiola Porro, Luisa Costessi, Martín L Marro, Francisco E Baralle, Andrés F Muro
    Abstract:

    The erythrocyte membrane cytoskeleton is organized as a polygonal spectrin network linked to short Actin filaments that are capped by adducin at the barbed ends. We have constructed a mouse strain deficient in beta-adducin having abnormal erythrocytes. We show here that the levels of several skeletal Proteins from beta-adducin mutant erythrocytes are altered. In fact, CapZ, the main muscle Actin-Capping Protein of the barbed ends that in the erythrocytes is cytoplasmic, is 9-fold upregulated in mutant skeletons of erythrocytes suggesting a compensatory mechanism. We also detected upregulation of tropomodulin and downregulation of alpha-tropomyosin and Actin. In addition, purified adducin can be re-incorporated into adducin-deficient ghosts.

  • The erythrocyte skeletons of β-adducin deficient mice have altered levels of tropomyosin, tropomodulin and EcapZ
    FEBS Letters, 2004
    Co-Authors: Fabiola Porro, Luisa Costessi, Martín L Marro, Francisco E Baralle, Andrés F Muro
    Abstract:

    The erythrocyte membrane cytoskeleton is organized as a polygonal spectrin network linked to short Actin filaments that are capped by adducin at the barbed ends. We have constructed a mouse strain deficient in β-adducin having abnormal erythrocytes. We show here that the levels of several skeletal Proteins from β-adducin mutant erythrocytes are altered. In fact, CapZ, the main muscle Actin-Capping Protein of the barbed ends that in the erythrocytes is cytoplasmic, is 9-fold upregulated in mutant skeletons of erythrocytes suggesting a compensatory mechanism. We also detected upregulation of tropomodulin and downregulation of α-tropomyosin and Actin. In addition, purified adducin can be re-incorporated into adducin-deficient ghosts.