SEARCH · PubMed Health

Results for “CapZ Actin Capping Protein”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources

PubMed2006

Control of cardiac myofilament activation and PKC-betaII signaling through the actin capping protein, CapZ.

Actin capping protein (CapZ) anchors the barbed ends of sarcomeric actin to the Z-disc. Myofilaments from transgenic mice (TG-CapZ) expressing a reduced amount of CapZ demonstrate altered function and protein kinase C (PKC) signaling [Pyle WG, Hart MC, Cooper JA, Sumandea MP, de Tombe PP, and Solaro RJ., Circ. Res. 90 (2002) 1299-306]. The aims of the current study were to determine the direct effects of CapZ on myofilament function and on PKC signaling to the myofilaments. Our studies compared mechanical properties of single myocytes from TG-CapZ mouse hearts to wild-type myocytes from which CapZ was extracted using PIP(2). We found that myofilaments from CapZ-deficient transgenic myocardium exhibited increased Ca(2+) sensitivity and maximum isometric tension. The extraction of CapZ from wild-type myofilaments replicated the increase in maximum isometric tension, but had no effect on myofilament Ca(2+) sensitivity. Immunoblot analysis revealed that the extraction of CapZ was associated with a reduction in myofilament-associated PKC-beta(II) and that CapZ-deficient transgenic myofilaments also lacked PKC-beta(II). Treatment of wild-type myofilaments with recombinant PKC-beta(II) reduced myofilament Ca(2+) sensitivity, whereas this effect was attenuated in myofilaments from TG-CapZ mice. Our results indicate that cardiac CapZ directly controls maximum isometric tension generation, and establish CapZ as an important component in anchoring PKC-beta(II) at the myofilaments, and for mediating the effects of PKC-beta(II) on myofilament function.

Actin Cytoskeleton↗

PubMed2003

Linking the T cell surface protein CD2 to the actin-capping protein CAPZ via CMS and CIN85.

Recruitment of CD2 to the immunological synapse in response to antigen is dependent on its proline-rich cytoplasmic tail. A peptide from this region (CD2:322-339) isolated CMS (human CD2AP); a related protein, CIN85; and the actin capping protein, CAPZ from a T cell line. In BIAcore analyses, the N-terminal SH3 domains of CMS and CIN85 bound CD2:322-339 with similar dissociation constants (KD = approximately 100 microm). CAPZ bound the C-terminal half of CMS and CIN85. Direct binding between CMS/CIN85 and CAPZ provides a link with the actin cytoskeleton. Overexpression of a fragment from the C-terminal half or the N-terminal SH3 domain of CD2AP in a mouse T cell hybridoma resulted in enhanced interleukin-2 production and reduced T cell receptor down-modulation in response to antigen. These adaptor proteins are important in T cell signaling consistent with a role for CD2 in regulating pathways initiated by CMS/CIN85 and CAPZ.

Adaptor Proteins, Signal Transducing↗

PubMed1996

Interaction of S100a0 protein with the actin capping protein, CapZ: characterization of a putative S100a0 binding site in CapZ alpha-subunit.

S100a0, a Ca2+-binding protein expressed predominantly in cardiac and skeletal muscle tissues, was demonstrated by chemical cross-linking to interact in a Ca2+ -dependent manner with the actin capping protein CapZ. TRTK-12, a peptide contained within the COOH-terminal region of CapZalpha, inhibited S100a0: CapZ interaction in a dose-dependent manner. TRTK-12 was shown by cross-linking to bind S100a0 in the presence of Ca2+, and by fluorescence spectrophotometry to interact in a saturable manner with the anionic phospholipid and a regulator of CapZ activity, phosphatidylinositol 4-monophosphate; but not with the neutral phospholipid, phosphatidylcholine. These data suggest S100a0 and polyphosphoinositides bind to the same COOH-terminal region of CapZalpha, thus potentially modulating CapZ activity.

Amino Acid Sequence↗

PubMed1997

Identification of the binding site on S100B protein for the actin capping protein CapZ.

The calcium-binding protein S100B binds to several potential target proteins, but there is no detailed information showing the location of the binding site for any target protein on S100B. We have made backbone assignments of the calcium-bound form of S100B and used chemical-shift changes in spectra of 15N-labeled protein to locate the site that binds a peptide corresponding to residues 265-276 from CapZ alpha, the actin capping protein. The largest chemical-shift changes are observed for resonances arising from residues around the C terminus of the C-terminal helix of S100B and residues Val-8 to Asp-12 of the N-terminal helix. These residues are close to but not identical to residues that have been identified by mutational analysis to be important in other S100 protein-protein interactions. They make up a patch across the S100B dimer interface and include some residues that are quite buried in the structure of calcium-free S100B. We believe we may have identified a binding site that could be common to many S100 protein-protein interactions.

Amino Acid Sequence↗

PubMed1995

Characterization of S-100b binding epitopes. Identification of a novel target, the actin capping protein, CapZ.

Short amino acid sequences that interact with the Ca2+ binding protein S-100b were identified by screening a bacteriophage random peptide display library. S-100b binding bacteriophages were selected by Ca(2+)-dependent affinity chromatography, and the sequence of the random peptide insert contained in 51 clones was determined. Alignment of the sequence of 44 unique S-100b binding peptides identified a common motif of eight amino acids. A subgroup of peptides that contained sequences with the highest degree of similarity had the consensus motif (K/R)(L/I)XWXXIL, in which predominantly P, S, and N were found in position 3, and S and D were found in position 5. Analysis of sequence databanks identified a similar sequence in the COOH-terminal region of the alpha-subunit of actin capping proteins. The peptide TRTKIDWNKILS (TRTK-12), corresponding to the region of greatest homology within this region of the subunit of actin capping proteins (e.g. amino acids 265-276 in CapZ alpha 1 and CapZ alpha 2), was synthesized and shown by fluorescence spectrophotometry to bind S-100b in a Ca(2+)-dependent manner. Gel overlay and cross-linking experiments demonstrated the interaction of S-100b with CapZ to be Ca2+ dependent. Moreover, this interaction was blocked by addition of TRTK-12 peptide. These results identify Ca(2+)-dependent S-100b target sequence epitopes and designate the carboxyl terminus of the alpha-subunit of actin capping proteins, like CapZ, to be a target of S-100b activity. The high level of conservation within this region of actin capping proteins and the apparent high affinity of this interaction strongly suggest that the interaction between S-100b and the alpha-subunit of actin capping proteins is biologically significant.

Amino Acid Sequence↗

PubMed1999

Effect of capping protein, CapZ, on the length of actin filaments and mechanical properties of actin filament networks.

We report on how physiological concentrations of capping protein shorten actin filaments and on the remarkably fluid nature of solutions of such short filaments even at the high concentrations that exist in cells. We measured the lengths of actin filaments formed by spontaneous polymerization of highly purified actin monomers by fluorescence microscopy after labeling with rhodamine-phalloidin. The length distributions are exponential with a mean of about 7 microm (2600 subunits). As observed previously with less quantitative assays, copolymerization with the actin capping protein, CapZ, reduces the length of the filaments. At cellular concentrations of capping protein, one filament forms for each molecule of capping protein and the population of filaments is uniformly short. Using CapZ to vary the length of actin filaments, we measured how their mechanical properties depend on length. The stiffness (elastic modulus) of actin filament networks depends steeply on the length, with long filaments contributing far out of proportion to their numbers to the stiffness. Even at physiological concentrations (300 microM), networks of filaments limited to lengths observed in cells with a 1 to 500 molar ratio of CapZ are more fluid and much less elastic than lower concentrations of longer actin filaments. Thus the high concentration of short actin filaments in cells must be crosslinked to produce the observed stiffness of the cortex.

Actins↗

PubMed1999

Role of the C-terminal extension in the interaction of S100A1 with GFAP, tubulin, the S100A1- and S100B-inhibitory peptide, TRTK-12, and a peptide derived from p53, and the S100A1 inhibitory effect on GFAP polymerization.

Whereas native and recombinant S100A1 inhibited GFAP assembly, a truncated S100A1 lacking the last six C-terminal residues (Phe88-Ser93) (S100A1Delta88-93) proved unable to do so. The inhibitory effects of native and recombinant S100A1 on GFAP assembly were blocked by both TRTK-12, a synthetic peptide derived from the alpha-subunit of the actin capping protein, CapZ, and a synthetic peptide derived from the tumor-suppressor protein, p53, in a dose-dependent manner. By fluorescent spectroscopy, TRTK-12 and the p53 peptide, like GFAP and tubulin, caused a dose- and Ca2+-dependent blue-shift of the fluorescence maximum of acrylodan-S100A1. In contrast, GFAP, tubulin, TRTK-12, or the p53 peptide caused no significant changes in the fluorescence spectrum of acrylodan-S100A1Delta88-93. By chemical crosslinking, both TRTK-12 and the p53 peptide strongly reduced or blocked the formation of GFAP-S100A1 or tubulin-S100A1 complexes, respectively, and S100A1Delta88-93 was unable to complex with tubulin, whereas a remarkably reduced complexation of GFAP with the truncated protein was observed. All the above observations show that the C-terminal extension of S100A1 is an essential part of the S100A1 site implicated in the recognition of GFAP, tubulin, p53, and the alpha-subunit of CapZ.

Animals↗

PubMed1998

Hydrophobic residues in the C-terminal region of S100A1 are essential for target protein binding but not for dimerization.

S100 proteins are a family of small dimeric proteins characterized by two EF hand type Ca2+ binding motifs which are flanked by unique N- and C-terminal regions. Although shown unequivocally in only a few cases S100 proteins are thought to function by binding to, and thereby regulating, cellular target proteins in a Ca2+ dependent manner. To describe for one member of the family, S100A1, structural requirements underlying target protein binding, we generated specifically mutated S100A1 derivatives and characterized their interaction with the alpha subunit of the actin capping protein CapZ shown here to represent a direct binding partner for S100A1. Chemical cross-linking, ligand blotting and fluorescence emission spectroscopy reveal that removal of, or mutations within, the sequence encompassing residues 88-90 in the unique C-terminal region of S100A1 interfere with binding to CapZ alpha and to TRTK-12, a synthetic CapZ alpha peptide. The S100A1 sequence identified contains a cluster of three hydrophobic residues (Phe-88, Phe-89 and Trp-90) at least one of which--as revealed by qualitative phenyl Sepharose binding and hydrophobic fluorescent probe spectroscopy--is exposed on the protein surface of Ca2+ bound S100A1. As homologous hydrophobic residues in the closely related S100B protein were shown by NMR spectroscopy of Ca(2+)-free S100B dimers to provide intersubunit contacts [Kilby P.M., van Eldik L.J., Roberts G.C.K. The solution structure of the bovine S100B dimer in the calcium-free state. Structure 1996; 4: 1041-1052; Drohat A.C., Amburgey J.C., Abildgaard F., Starich M.R., Baldisseri D., Weber D.J. Solution structure of rat apo-S100B (beta beta) as determined by NMR spectroscopy. Biochemistry 1996; 35: 11,577-11,588], we characterized the physical state of the various S100A1 derivatives. Analytical gel filtration and chemical cross-linking show that dimer formation is not compromised in S100A1 mutants lacking residues 88-90 or containing specific amino acid substitutions in this sequence. Thus a cluster of hydrophobic residues in the C-terminal region of S100A1 is essential for target protein binding but dispensable for dimerization, a situation possibly met in other S100 proteins as well.

Amino Acid Sequence↗

PubMed2003

Interactions between the evolutionarily conserved, actin-related protein, Arp11, actin, and Arp1.

The dynein activator dynactin is a multiprotein complex with distinct microtubule- and cargo-binding domains. The cargo-binding domain contains a short, actin-like filament of the actin-related protein Arp1, a second actin-related protein, Arp11, and conventional actin. The length of this filament is invariant in dynactin isolated from multiple species and tissues, suggesting that activities that regulate Arp1 polymerization are important for dynactin assembly. Arp11 is present in a protein complex localized at the pointed end of the Arp1 minifilament, whereas actin capping protein (CapZ) is present at the barbed end. Either might cooperate with conventional actin to cap Arp1. We tested the ability of Arp11 to interact with conventional actin and found it could coassemble. Like Arp1, cytosolic Arp11 is found only in dynactin, suggesting that Arp11 and free cytosolic actin do not interact significantly. Recombinant Arp11 and Arp1 were demonstrated to interact by coprecipitation. We developed an in vivo assay for Arp11-Arp1 interaction based on previous observations that Arp1 forms filamentous assemblies when overexpressed in cultured cells. Arp11 significantly decreases the formation of these organized Arp1 assemblies. Finally, this assay was used to confirm the identity of a putative Arp11 homolog in Drosophila melanogaster.

Actin-Related Protein 3↗

PubMed1996

Purification and properties of a Ca(2+)-independent barbed-end actin filament capping protein, CapZ, from human polymorphonuclear leukocytes.

In human polymorphonuclear leukocytes (PMN), changes in the actin architecture are critical for the shape changes required for chemotaxis and phagocytosis. Barbed-end capping proteins are likely to regulate actin assembly in PMN. The previously identified barbed-end blocking proteins in PMN, gelsolin and CapG, require Ca(2+) to initiate capping of actin filaments. Because chemoattractants can stimulate PMN actin assembly by a calcium-independent signal transduction pathway, we sought to purify a calcium-independent barbed-end capping activity from PMN cytoplasmic extracts. A Ca(2+) -insensitive actin polymerization inhibitory activity was partially purified from human PMN [Southwick & Stossel (1981) J. Biol. Chem 256, 3030]. Using five column chromatography steps, we purified the protein to homogeneity as assessed by silver staining. Purification was associated with an increase in specific activity of greater than 40 X. Western blot analysis identified the protein as the nonmuscle isoform of the heterodimeric capping protein capZ. Human PMN capZ has an apparent disassociation constant of 3 nM for capping in the presence or absence of micromolar Ca(2+), as assessed by both pyrenylactin elongation and depolymerization assays. Similar to the activity reported for the actin polymerization inhibitor, activity of PMN capZ was inhibited by increasing the KC1 concentration from 0.1 M to 0.6 M. The capping function was also inhibited by phosphatidylinositol 4,5-bisphosphate (PIP(2)) micelles, with half-maximal inhibition occurring at 5.5 micrograms mL(-1). PMN capZ did not nucleate actin assembly, sequester actin monomers, or sever actin filaments. Quantitative Western blot analysis revealed that capZ levels corresponded to 0.7-1.0% of the total human PMN cytoplasmic protein. Given its abundance and high affinity for barbed filament ends, capZ is likely to play an important role in the calcium-independent regulation of actin filament assembly associated with PMN chemotaxis.

Actin Cytoskeleton↗

PubMed2002

Actin capping protein: an essential element in protein kinase signaling to the myofilaments.

Actin capping protein (CapZ) binds the barbed ends of actin at sarcomeric Z-lines. In addition to anchoring actin, Z-discs bind protein kinase C (PKC). Although CapZ is crucial for myofibrillogenesis, its role in muscle function and intracellular signaling is unknown. We hypothesized that CapZ downregulation would impair myocardial function and disrupt PKC-myofilament signaling by impairing PKC-Z-disc interaction. To test these hypotheses, we examined transgenic (TG) mice in which cardiac CapZ protein is reduced. Fiber bundles were dissected from papillary muscles and detergent extracted. Some fiber bundles were treated with PKC activators phenylephrine (PHE) or endothelin (ET) before detergent extraction. We simultaneously measured Ca2+-dependent tension and actomyosin MgATPase activity. CapZ downregulation increased myofilament Ca2+ sensitivity without affecting maximum tension or actomyosin MgATPase activity. Maximum tension and actomyosin MgATPase activity were decreased after PHE or ET treatment of wild-type (WT) muscle. Fiber bundles from TG hearts did not respond to PHE or ET. Immunoblot analysis revealed an increase in myofilament-associated PKC-epsilon after PHE or ET exposure of WT preparations. In contrast, myofilament-associated PKC-epsilon was decreased after PHE or ET treatment in TG myocardium. Protein levels of myofilament-associated PKC-beta were decreased in TG ventricle. C-protein and troponin I phosphorylation was increased after PHE or ET treatment in WT and TG hearts. Basal phosphorylation levels of C-protein and troponin I were higher in TG myocardium. These results indicate that downregulation of CapZ, or other changes associated with CapZ downregulation, increases cardiac myofilament Ca2+ sensitivity, inhibits PKC-mediated control of myofilament activation, and decreases myofilament-associated PKC-beta.

Actin Cytoskeleton↗

PubMed1991

Regulation of CapZ, an actin capping protein of chicken muscle, by anionic phospholipids.

Chicken muscle CapZ, a member of the capping protein family of actin-binding proteins, binds to the barbed end of actin filaments and nucleates actin polymerization. No regulation of the capping protein family has been described. We report that micelles of phosphatidylinositol 4,5-bisphosphate (PIP2) bind to CapZ and completely inhibit its ability to affect actin polymerization as measured by several independent assays. Higher concentrations of other anionic phospholipids also completely inhibit the activity of CapZ. Neutral phospholipids have no effect. Mixed vesicles of PIP2 with phosphatidylcholine or phosphatidylethanolamine also inhibit CapZ, but addition of Triton X-100 both prevents and reverses PIP2's inhibition of CapZ.

Actin Capping Proteins↗

PubMed2003

Regulation of sodium channel activity by capping of actin filaments.

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.

Actins↗

PubMed1989

Effects of CapZ, an actin capping protein of muscle, on the polymerization of actin.

We have studied the interaction of CapZ, a barbed-end actin capping protein from the Z line of skeletal muscle, with actin. CapZ blocks actin polymerization and depolymerization (i.e., it "caps") at the barbed end with a Kd of approximately 0.5-1 nM or less, measured by three different assays. CapZ inhibits the polymerization of ATP-actin onto filament ends with ATP subunits slightly less than onto ends with ADP subunits, and onto ends with ADP-BeF3- subunits about as much as ends with ADP subunits. No effect of CapZ is seen at the pointed end by measurements either of polymerization from acrosomal processes or of the critical concentration for polymerization at steady state. CapZ has no measureable ability to sever actin filaments in a filament dilution assay. CapZ nucleates actin polymerization at a rate proportional to the first power of the CapZ concentration and the 2.5 power of the actin concentration. No significant binding is observed between CapZ and rhodamine-labeled actin monomers by fluorescence photobleaching recovery. These new experiments are consistent with but do not distinguish between three models for nucleation proposed previously (Cooper & Pollard, 1985). As a prelude to the functional studies, the purification protocol for CapZ was refined to yield 2 mg/kg of chicken breast muscle in 1 week. The activity is stable in solution and can be lyophilized. The native molecular weight is 59,600 +/- 2000 by equilibrium ultracentrifugation, and the extinction coefficient is 1.25 mL mg-1 cm-1 by interference optics. Polymorphism of the alpha and beta subunits has been detected by isoelectric focusing and reverse-phase chromatography. CapZ contains no phosphate (less than 0.1 mol/mol).

Actins↗

PubMed2005

The phosphorylation of CapZ-interacting protein (CapZIP) by stress-activated protein kinases triggers its dissociation from CapZ.

A protein expressed in immune cells and muscle was detected in muscle extracts as a substrate for several SAPKs (stress-activated protein kinases). It interacted specifically with the F-actin capping protein CapZ in splenocytes, and was therefore termed 'CapZIP' (CapZ-interacting protein). Human CapZIP was phosphorylated at Ser-179 and Ser-244 by MAPKAP-K2 (mitogen-activated protein kinase-activated protein kinase 2) or MAPKAP-K3 in vitro. Anisomycin induced the phosphorylation of CapZIP at Ser-179 in Jurkat cells, which was prevented by SB 203580, consistent with phosphorylation by MAPKAP-K2 and/or MAPKAP-K3. However, osmotic shock-induced phosphorylation of Ser-179 was unaffected by SB 203580. These and other results suggest that CapZIP is phosphorylated at Ser-179 in cells by MAPKAP-K2/MAPKAP-K3, and at least one other protein kinase. Stress-activated MAP kinase family members phosphorylated human CapZIP at many sites, including Ser-68, Ser-83, Ser-108 and Ser-216. Ser-108 became phosphorylated when Jurkat cells were exposed to osmotic shock, which was unaffected by SB 203580 and/or PD 184352, or in splenocytes from mice that do not express either SAPK3/p38gamma or SAPK4/p38delta. Our results suggest that CapZIP may be phosphorylated by JNK (c-Jun N-terminal kinase), which phosphorylates CapZIP to >5 mol/mol within minutes in vitro. Osmotic shock or anisomycin triggered the dissociation of CapZIP from CapZ in Jurkat cells, suggesting that phosphorylation of CapZIP may regulate the ability of CapZ to remodel actin filament assembly in vivo.

Actins↗

PubMed2002

Solution NMR structure of S100B bound to the high-affinity target peptide TRTK-12.

The solution NMR structure is reported for Ca(2+)-loaded S100B bound to a 12-residue peptide, TRTK-12, from the actin capping protein CapZ (alpha1 or alpha2 subunit, residues 265-276: TRTKIDWNKILS). This peptide was discovered by Dimlich and co-workers by screening a bacteriophage random peptide display library, and it matches exactly the consensus S100B binding sequence ((K/R)(L/I)XWXXIL). As with other S100B target proteins, a calcium-dependent conformational change in S100B is required for TRTK-12 binding. The TRTK-12 peptide is an amphipathic helix (residues W7 to S12) in the S100B-TRTK complex, and helix 4 of S100B is extended by three or four residues upon peptide binding. However, helical TRTK-12 in the S100B-peptide complex is uniquely oriented when compared to the three-dimensional structures of other S100-peptide complexes. The three-dimensional structure of the S100B-TRTK peptide complex illustrates that residues in the S100B binding consensus sequence (K4, I5, W7, I10, L11) are all involved in the S100B-peptide interface, which can explain its orientation in the S100B binding pocket and its relatively high binding affinity. A comparison of the S100B-TRTK peptide structure to the structures of apo- and Ca(2+)-bound S100B illustrates that the binding site of TRTK-12 is buried in apo-S100B, but is exposed in Ca(2+)-bound S100B as necessary to bind the TRTK-12 peptide.

Amino Acid Sequence↗

PubMed2000

Interaction of actin with the capping protein, CapZ from sea bass (Dicentrarchus labrax) white skeletal muscle.

We have compared the functional properties of CapZ from fish white skeletal muscle with those of CapZ from chicken muscle. CapZ is a heterodimer, which enhances actin nucleation and inhibits the depolymerization process by binding to the barbed ends of microfilaments. Here, we report the interaction of CapZ not only with F-actin, but also with monomeric actin. The affinity of sea bass CapZ for G-actin estimated by enzyme-linked immunosorbent assay (ELISA) was in the microM range. This association was PIP2 dependent. Binding contacts with the barbed end of actin were delimited by both ELISA and fluorescence approaches. One site (actin sequence 338-348) was located in a helical region of the subdomain 1, region already implicated in the interaction with other actin binding proteins such as gelsolin. Another site implicates the C-terminal region (sequence 360-372) of actin. Finally, the partial competition of antibodies directed against CapZ alpha or beta-subunits towards CapZ interaction with actin filaments suggests both subunits participate in the complex with actin.

Actins↗

PubMed2004

Searching for the missing link: a role for the actin capping protein in heart failure.

Cardiac Z-discs have historically been classified as passive myocardial elements. Z-discs are positioned at the junction between the cytoskeleton and the myofilaments, providing a physical connection between the sarcomere, nucleus, membrane and sarcoplasmic reticulum. Moreover, numerous molecular messengers congregate at the Z-disc. The combination of physical and chemical signals moving through the Z-disc makes this myocardial element a vital switching station of the heart, and suggests significant regulatory potential. Using the actin capping protein (CapZ) as a representative of the Z-disc, it was found that decreasing CapZ enhances force development and inhibits protein kinase C, a messenger of heart failure. These results indicate the potential for CapZ as a therapeutic target in the management of heart failure. Future research is required to determine the mechanisms by which changes in CapZ impact myocardial function and intracellular signalling, and to develop feasible strategies that can manipulate CapZ in the intact heart.

Actin Capping Proteins↗