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Query: UNIPROT:Q9Y573 (actin-binding protein)
 1,734 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The role of platelets in hemostasis and thrombosis has been well established since Eberth's and Schimmelbusch's pioneering intravital microscopic experiments. A century ago the distinct features of the circulating "smooth disc" and the activated "spiny sphere" were described. Since then the underlying cell-biological processes transforming a harmless floating platelet into a sticky corpuscle, ready to release its stores of thrombogenic and atherogenic substances have been unveiled. However, its life-threatening capabilities have evolved from the necessity of preventing equally dangerous blood losses from a pressurized circulation system. As circulation depends on the liquid state of blood, the platelets and the molecules of the plasmatic coagulation system must circulate in an inactive state, to become activated at the site of "demand" to transform the liquid into a solid hemostatic plug. As in nucleated cells the plasma membrane, made up of a phospholipid bilayer with integrated glycoproteins, is the structure signalling environmental information to the platelet interior. Many of the receptors for stimulatory or inhibitory mediators elicit a cell-biological response via G-proteins and subsequent Ca2+ mobilization by IP3, or stimulation/inhibition of adenylate cyclase followed by changes in cytoplasmic levels of cyclic AMP. The supposed intracellular Ca2+ store of the platelets, the dense tubular system, also appears as the site of Ca2(+)-activated prostaglandin synthesis. Raised cytoplasmic Ca2+ levels promote the polymerization of G-actin to F-actin involved in the extension of pseudopodia in the course of "external shape change." Ca2(+)-activated myosin light-chain kinase phosphorylates myosin which becomes associated with F-actin, with the resulting acto-myosin complex providing the contractile force for "internal shape change," i.e., the centralization of organelles and for clot retraction later in hemostasis. More than by the three-dimensional actin cytoskeleton proper, the discoid shape typical of the nonstimulated platelet appears to be secured by a two-dimensional membrane skeleton of actin filaments anchored to membrane glycoproteins via actin-binding protein or spectrin and ankyrin. Although the microtubule coil has been confirmed as the main determinant of the mechanical stiffness of the platelet with biophysical techniques, its hitherto assumed role for the maintenance of the disc shape no longer appears tenable. The morphological phenomenon of the shape change comprises an alteration of membrane glycoproteins resulting in binding of "adhesive" molecules like fibrinogen.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Histophysiology of the circulating platelet. 226

Time course change of the platelet cytoskeletal protein component in the Triton X-100 insoluble fraction after stimulation was analyzed in Hermansky-Pudlak syndrome and thrombasthenia. In Hermansky-Pudlak syndrome (HPS), a 31 kDa protein, myosin, actin, and a 100 kDa protein assembled as in the normal platelets at the shape change and release reaction phases after ADP or collagen stimulation, suggesting that, the deficient dense granule content do not lead to an abnormal platelet cytoskeletal protein assembly. In thrombasthenia (Type I), myosin increased at the shape change and release reaction phases as it does in normal platelets, but actin and the 100 kDa protein increased only at the initial activation phase, and then subsequently decreased to the level of the resting phase. The actin-binding protein (ABP) and the 31 kDa protein increased a little following stimulation. Similar cytoskeletal protein change after stimulation were found in normal platelets which were prevented from the aggregation process by chelating the external Ca2+ or by using synthetic decapeptide of fibrinogen gamma-chain of carboxyl terminus. The decreased platelet cytoskeletal protein assembly in thrombasthenia or in platelets stimulated without aggregation, was derived from a loss of the platelet aggregation process due to the defect of GP IIb-IIIa complex or an interaction failure between GP IIb-IIIa complex and fibrinogen. The interaction between platelets and either fibrinogen or fibrin can induce a more stable platelet cytoskeletal protein assembly, however, agonistic stimulation without these interactions cannot do it directly.
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PMID:Analysis of platelet cytoskeleton assembly during platelet activation in Hermansky-Pudlak syndrome and thrombasthenia. 233 46

In yeast, the cortical actin cytoskeleton seems to specify sites of growth of the cell surface. Because the actin-binding protein ABP1p is associated with the cortical cytoskeleton of Saccharomyces cerevisiae, it might be involved in the spatial organization of cell surface growth. ABP1p is localized to the cortical cytoskeleton and its overproduction causes assembly of the cortical actin cytoskeleton at inappropriate sites on the cell surface, resulting in delocalized surface growth. We have now cloned and sequenced the gene encoding ABP1p. ABP1p is a novel protein with a 50 amino-acid C-terminal domain that is very similar to the SH3 domain in the non-catalytic region of nonreceptor tyrosine kinases (including those encoded by the proto-oncogenes c-src and c-abl), in phospholipase C gamma and in alpha-spectrin. We also identified an SH3-related motif in the actin-binding tail domain of myosin-I. The identification of SH3 domains in a family of otherwise unrelated proteins that associate with the membrane cytoskeleton indicates that this domain might serve to bring together signal transduction proteins and their targets or regulators, or both, in the membrane cytoskeleton.
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PMID:Homology of a yeast actin-binding protein to signal transduction proteins and myosin-I. 240 79

Triton-insoluble cytoskeletons were isolated from Dictyostelium discoideum AX3 cells prior to and following stimulation with 2'deoxy cyclic adenosine monophosphate (cAMP). Temporal changes in the content of actin and a 120,000 dalton actin-binding protein (ABP-120) in cytoskeletons following stimulation were monitored. Both actin and ABP-120 were incorporated into the cytoskeleton at 30-40 seconds following stimulation, which is cotemporal with the onset of pseudopod extension during stimulation of amoebae with chemoattractants. Changes in the content of total cytoskeletal protein and cytoskeletal myosin were determined under the same experimental conditions as controls. These proteins exhibited different kinetics from those of cytoskeletal ABP-120 and actin following the addition of 2'deoxy cAMP. The authors concluded that the association of ABP-120 with the cytoskeleton is regulated during cAMP signalling. Furthermore, these results indicate that ABP-120 is involved in cross-linking newly assembled actin filaments into the cytoskeleton during chemoattractant-stimulated pseudopod extension.
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PMID:Changes in the association of actin-binding proteins with the actin cytoskeleton during chemotactic stimulation of Dictyostelium discoideum. 254 8

Blood platelets are particularly rich in cytoskeletal proteins and respond to stimulation and activation by changes in shape. We examined the effect of blood platelet activation on the subcellular distribution of the cytoskeletal proteins, actin, myosin, alpha-actinin and actin-binding protein. These studies were performed with immunofluorescent staining on thin cryosections of paraformaldehyde-fixed platelets and by immunogold labeling of ultrathin cryosections of glutaraldehyde-fixed blood platelets. Platelets were studied immediately at blood collection (resting platelets), in platelet-rich plasma and after gel filtration (partially activated platelets), and after gel filtration and thrombin activation (0.5 U/ml, 10 min, 37 degrees C) (activated platelets). Resting platelets were disk-shaped and showed homogeneous distribution of cytoskeletal proteins. Partially activated platelets were more spherical and showed at least one protrusion. Immunofluorescence and immunogold labeling showed a more intense staining of the peripheral 0.2 to 0.3 micron of cytoplasm of these platelets. In the immunofluorescence photographs this resulted in the appearance of small fluorescent rings with staining at the periphery of cross-sectioned cells. Activated platelets showed an irregular outline composed of broad based pseudopods. Cell centers were composed of poorly delineated electron-dense material, interspersed with profiles of surface-connected tubules. The broad based pseudopods stained uniformely for actin, alpha-actinin and actin-binding protein. The cell center stained poorly for these proteins. Myosin staining was found in the peripheral cortex, but also in the cell center. Partially activated platelets that had returned to the disk shape after incubation at 37 degrees C showed increased submembranous concentration of microfilament proteins. These data reveal the profound cytoskeletal rearrangements that already occur upon minimal platelet activation and emphasize that platelets that have returned to the disk shape are not identical to resting platelets.
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PMID:Immunoelectron microscopic localization of actin, alpha-actinin, actin-binding protein and myosin in resting and activated human blood platelets. 274 1

Immunolocalization of monoclonal antibodies to Acanthamoeba myosin I showed a cross-reactive protein in nuclei (Hagen, S. J., D. P. Kiehart, D. A. Kaiser, and T. D. Pollard. 1986. J. Cell Biol. 103:2121-2128). This protein is antigenically related to myosin I in that nine monoclonal antibodies and three polyclonal antibodies are cross-reactive. However, studies with affinity-purified antibodies and two-dimensional peptide maps show that the protein is not a proteolytic product of myosin I. We have used cell fractionation and column chromatography to purify this protein. It is a dimer of 34-kD polypeptides with a Stokes' radius of 4 nm. A polyclonal antisera generated against the purified protein confirms the nuclear localization seen with the cross-reactive monoclonal antibodies. The 34-kD protein binds actin filaments in an ATP-insensitive manner with a Kd of approximately 0.25 microM without cross-linking, severing, or capping. No ATPase activity was detected in the presence or absence of actin. It also binds to DNA. These unique properties suggest we have discovered a new class of actin-binding protein. We have given this protein the name NAB for "nuclear actin-binding" protein.
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PMID:Purification and characterization of an Acanthamoeba nuclear actin-binding protein. 276 Jan 8

Caldesmon is a major calmodulin- and actin-binding protein of smooth muscle which interacts with calmodulin in a Ca2+-dependent manner or with actin in a Ca2+-independent manner. Isolated caldesmon is capable of inhibiting the actin-activated Mg2+-ATPase of smooth-muscle myosin, suggesting a possible physiological role for caldesmon in regulating the contractile state of smooth-muscle. Caldesmon can be phosphorylated in vitro by a co-purifying Ca2+/calmodulin-dependent protein kinase and dephosphorylated by a protein phosphatase, both of which are present in smooth muscle. We investigated further the phosphorylation of caldesmon and the effects which phosphorylation has on the functional properties of the protein. The kinetics of caldesmon phosphorylation were similar whether the caldesmon substrate was free or bound to actin, actin/tropomyosin or thin filaments. Caldesmon containing endogenous kinase activity was rapidly phosphorylated (to approx. 1 mol of Pi/mol of caldesmon in 5 min) when reconstituted with actin, myosin, tropomyosin, calmodulin and myosin light-chain kinase in the presence of Ca2+ and MgATP2-. Under conditions in which unphosphorylated caldesmon showed substantial inhibition of the actin-activated myosin Mg2+-ATPase, no inhibition was observed with phosphorylated caldesmon. This was the case whether caldesmon was phosphorylated before addition to the actomyosin Mg2+-ATPase system, or phosphorylation was allowed to take place during the ATPase reaction. Binding studies revealed maximal binding of 1 mol of unphosphorylated caldesmon/9.5 mol of actin and 1 mol of phosphorylated caldesmon/11.7 mol of actin. All the bound phosphorylated caldesmon could be released by Ca2+/calmodulin, with half-maximal release at 0.11 microM-Ca2+, whereas only 62% of the bound unphosphorylated caldesmon could be removed, with half-maximal release at 0.16 microM-Ca2+. However, under conditions in which inhibition of actomyosin Mg2+-ATPase activity by non-phosphorylated but not by phosphorylated caldesmon was observed, both forms of caldesmon would remain bound to the thin filament. These observations suggest a possible mechanism whereby caldesmon phosphorylation may prevent its inhibitory action on the actomyosin Mg2+-ATPase.
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PMID:The effects of phosphorylation of smooth-muscle caldesmon. 282 3

Triton X-100 residues (cytoskeletons) of human platelets were prepared in the presence of various concentrations of free calcium (Ca2+), and the polypeptide composition and ATPase activity were examined. Triton residues prepared in the presence of Ca2+ concentrations below 2 X 10(-7) M were composed primarily of polypeptides with an apparent molecular mass of 43 (actin), 105 (alpha-actinin-like protein) and 250 (actin-binding protein) kDa and showed low K+-EDTA-ATPase activity. When Triton residues were prepared at Ca2+ above 5 X 10(-7) M, a 200 kDa polypeptide (myosin heavy chain) and K+-EDTA-ATPase activity increased markedly, but actin-binding protein and alpha-actinin-like protein decreased. When N-(N-(L-3-trans-carboxyoxirane-2-carbonyl)-L-leucyl)agmatine, an inhibitor for Ca2+-dependent proteinase, was added to Triton lysis buffer containing high Ca2+, polypeptides of 250, 235 and 105 kDa remained associated with the residues. Under electron microscopic analysis, the treatment of platelets with Triton X-100 at low Ca2+ showed a network of microfilaments. When platelets were treated with high Ca2+, the microfilaments were disrupted and a few thick filaments and many granules appeared. However, when the inhibitor for Ca2+-proteinase was included in Triton lysis buffer, the microfilaments remained intact. These results suggested that an increase in Ca2+ concentration to more than 5 X 10(-7) M not only makes myosin associate with cytoskeletons but also regulates the organization of filamentous structures.
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PMID:Effect of calcium on protein composition of human platelet cytoskeletons. 293 Nov 20

Both fluorescence microscopy and fluorometric analysis techniques have been used to characterize insulin receptor capping in IM-9 human lymphoblastoid cells. Morphologically, insulin caps appear similar to lectin or antiimmunoglobulin-induced caps displaying a preferential accumulation of actin, myosin, and actin-binding protein directly underneath the cap structure. Using the fluorescent calcium indicator quin2 we have detected no change in the calcium activity following insulin stimulation. However, in the presence of a number of calmodulin inhibitors, such as W-5, W-7, W-12, and trifluoperazine (TFP), insulin capping is significantly inhibited, which implies that a calmodulin-regulated process is involved. Using double immunofluorescence microscopy, we have found that the calmodulin-dependent myosin light chain kinase (MLCK) is concentrated directly beneath insulin caps. Upon treatment with trifluoperazine (TFP), the redistribution of both MLCK and insulin receptors are inhibited concomitantly. Our data indicate that the calmodulin-dependent myosin light chain kinase may be directly responsible for the activation of actomyosin-mediated contractility during insulin receptor capping.
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PMID:Insulin receptor capping and its correlation with calmodulin-dependent myosin light chain kinase. 293 41

Membrane-interacting amphiphiles, lysophosphatidylcholine, cepharanthine and chlorpromazine, inhibited concanavalin A (Con A)-induced platelet activation in a dose-dependent manner, as judged by the inhibition of serotonin release. These amphiphiles did not influence the binding of Con A to surface membrane glycoproteins. Marked increase in the amount of the cytoskeletal proteins, myosin, actin and actin-binding protein, in the Triton-insoluble residue of the Con A-activated platelets, as well as in the surface membrane glycoproteins with molecular weights of 224,000, 201,000, 119,000 and 92,000 found in the same residue, was inhibited by any of the three amphiphiles in a dose-dependent manner. Such inhibitory effect, however, was abolished when the amphiphiles were washed out from the platelets before the activation. These findings suggest that these membrane-interacting amphiphiles may inhibit the Con A-induced assembly of the cytoskeletal proteins and their association with surface membrane glycoproteins, probably by physically altering the membrane properties.
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PMID:Effect of membrane-interacting amphiphiles on association of membrane glycoproteins with assembled cytoskeletal proteins in concanavalin A-activated rabbit platelets. 294 Jul 28


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