Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q9Y573 (actin-binding protein)
 1,734 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A single-headed monomeric myosin (myosin I) was isolated from pig urinary bladder smooth muscles and purified to homogeneity. Myosin I from smooth muscle is composed of a 110-kDa heavy chain and three 17-kDa light chains. The heavy chain from smooth muscle myosin I does not cross-react with the antibody against conventional myosin (myosin II) from smooth muscle, but it does show antigenic similarity to adrenal medulla myosin I heavy chain. The light chain from smooth muscle myosin I is similar to calmodulin in molecular weight, amino acid composition, and migration on SDS-polyacrylamide gel electrophoresis in the presence of Ca2+. The high salt ATPase activity of myosin I in the presence of CaCl2 is higher than that in K(+)-EDTA. Smooth muscle actin causes a 5-10-fold activation of the Mg-ATPase activity of myosin I. In the presence of Ca2+, exogenous calmodulin enhances the actin-activated ATPase activity of myosin I, and the increased activity is associated with the binding of exogenous calmodulin to myosin I heavy chain. A maximum of 4 mol of light chains/mol of myosin I heavy chain is observed in the presence of exogenous calmodulin. Caldesmon, a calmodulin/actin-binding protein, inhibits the actin-activated ATPase activity of myosin I. This inhibition is reversed by exogenous calmodulin in the presence of Ca2+. The actin activation of myosin I ATPase exhibits around 50% Ca2+ sensitivity in the presence of exogenous calmodulin. When caldesmon is bound to actin, Ca2+ sensitivity is increased to 80% in the presence of calmodulin. Therefore, smooth muscle caldesmon, which is thought to play a role in the regulation of actin activation of myosin II, also regulates the actin activation of myosin I ATPase in smooth muscle.
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PMID:Myosin I from mammalian smooth muscle is regulated by caldesmon-calmodulin. 819 35

Caldesmon, an actin-binding protein from smooth muscle and non-muscle cells, has previously been shown to bind stoichiometrically to smooth muscle myosin in an ATP-dependent manner. We now show quantitatively the effects of Ca(2+)-calmodulin and phosphorylation on the binding of caldesmon to myosin. Ca(2+)-calmodulin reduces the binding of caldesmon to myosin with the same effectiveness as it does the binding of caldesmon to actin. However, Ca(2+)-calmodulin is ineffective in antagonizing the binding of the purified myosin-binding region of caldesmon to myosin. These and other results suggest that Ca(2+)-calmodulin binding to the COOH-terminal region of caldesmon is responsible for reversal of binding to myosin. Phosphorylation of the NH2-terminal region of caldesmon by the co-purifying kinase, calmodulin-dependent protein kinase II, weakens but does not eliminate the binding of caldesmon to smooth muscle myosin. Finally, phosphorylation of smooth muscle myosin by smooth muscle myosin light chain kinase has no effect on the binding of caldesmon to myosin. Since Ca(2+)-calmodulin and phosphorylation of caldesmon weaken the binding of caldesmon to both actin and myosin, these events may be coordinately regulated.
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PMID:Reversal of caldesmon binding to myosin with calcium-calmodulin or by phosphorylating caldesmon. 832

The mechanisms involved in the hemostatic abnormality of uremic patients remain obscure. We have explored the response of normal and uremic platelets to surface activation at the ultrastructural level and analyzed changes in the composition of proteins associated with normal and uremic platelet cytoskeletons after stimulation with thrombin (0.01 and 0.1 U/ml). Cytoskeletons were obtained by extraction with Triton X-100, processed by sodium dodecylsulfate-polyacrylamide gel electrophoresis, and the presence of cytoskeletal proteins analyzed by densitometry. Under static conditions, uremic platelets spread with difficulty on formvar-coated grids. The percentage of platelets that spread fully on this polymer surface was statistically reduced compared with that of control platelets (11 +/- 1.4 vs. 21 +/- 1.6; P < 0.05). An impairment of cytoskeletal organization was observed in resting uremic platelets but abnormalities were more evident after thrombin activation. The incorporation of actin into the cytoskeletons of thrombin-stimulated uremic platelets was significantly reduced with respect to controls (6 +/- 3% vs. 29 +/- 5%; P < 0.01 after 0.01 U/ml and 28 +/- 9% vs. 59 +/- 10%; P < 0.05 after 0.1 U/ml). Decreased associations of actin-binding protein (P < 0.01), alpha-actinin (P < 0.05), and tropomyosin (P < 0.05) with the cytoskeletons of uremic platelets were also noted. No difference was observed for the incorporation of myosin into the cytoskeletons of activated uremic platelets. These results suggest functional and biochemical alterations of the platelet cytoskeleton in uremia, which may contribute to the impairment of platelet function observed in uremic patients.
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PMID:Abnormal cytoskeletal assembly in platelets from uremic patients. 836 80

Coronin is an actin-binding protein in Dictyostelium discoideum that is enriched at the leading edge of the cells and in projections of the cell surface called crowns. The polypeptide sequence of coronin is distinguished by its similarities to the beta-subunits of trimeric G proteins (E. L. de Hostos, B. Bradtke, F. Lottspeich, R. Guggenheim, and G. Gerisch, 1991. EMBO (Eur. Mol. Biol. Organ.) J. 10:4097-4104). To elucidate the in vivo function of coronin, null mutants have been generated by gene replacement. The mutant cells lacking coronin grow and migrate more slowly than wild-type cells. When these cor- cells grow in liquid medium they become multinucleate, indicating a role of coronin in cytokinesis. To explore this role, coronin has been localized in mitotic wild-type cells by immunofluorescence labeling. During separation of the daughter cells, coronin is strongly accumulated at their distal portions including the leading edges. This contrasts with the localization of myosin II in the cleavage furrow and suggests that coronin functions independently of the conventional myosin in facilitating cytokinesis.
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PMID:Dictyostelium mutants lacking the cytoskeletal protein coronin are defective in cytokinesis and cell motility. 838 Jan 74

In resting platelets, the GPIb-IX complex, the receptor for the von Willebrand factor (vWF), is linked to underlying actin filaments by actin-binding protein (ABP-280). Thrombin stimulation of human platelets leads to a decrease in the surface expression of the GPIb-IX complex, which is redistributed from the platelet surface into the open canalicular system (OCS). Because the centralization of GPIb-IX is inhibited by cytochalasin, it is believed to be linked to actin cytoskeletal rearrangements that take place during platelet activation. We have further characterized the mechanism of GPIb-IX centralization in platelets in suspension. Following thrombin stimulation, GPIb-IX shifts from the membrane skeleton of the resting cell to the cytoskeleton of the activated cell in a reaction sensitive to cytochalasin B. The cytoskeletal association of GPIb-IX involves ABP-280, as it correlates with the incorporation of ABP-280 into the activated cytoskeleton and because no dissociation of the ABP-280/GPIb-IX complexes is detected after thrombin activation. However, the incorporation of GPIb-IX into the cytoskeleton is complete within 1 minute, whereas GPIb-IX centralization requires 5 to 10 minutes for completion. The movement of GPIb-IX to the cytoskeleton of activated platelets is therefore necessary, but not sufficient for GPIb-IX centralization. Blockage of cytosolic calcium increases induced by thrombin by loading with the cell permeant calcium chelator Quin-2 AM inhibited GPIb-IX centralization by 70%, but did not prevent its association with the activated cytoskeleton. Quin-2 loading did, however, decrease the incorporation of myosin II into the activated cytoskeleton. The role of myosin II was further probed using the myosin light chain kinase (MLCK) inhibitor wortmannin. Wortmannin prevents myosin II association to the activated cytoskeleton and inhibits GPIb-IX centralization by 50%, without affecting actin assembly or the association of GPIb-IX to the cytoskeleton. Only micromolar concentrations of wortmannin, high enough to inhibit MLCK, prevent GPIb-IX centralization. These results indicate that thrombin-induced GPIb-IX centralization requires a minimum of two steps, one associating GPIb-IX to the activated cytoskeleton and the second requiring myosin II activation. The involvement of myosin II implies that GPIb-IX/ABP-280 complexes, linked to actin filaments, are pulled into the cell center, and that platelets may exert contractile tension on vWF bound to its receptor.
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PMID:Thrombin-induced GPIb-IX centralization on the platelet surface requires actin assembly and myosin II activation. 855 84

Platelet function in 12 cancer patients was studied sequentially over 97 hr of interleukin-6 (IL-6) daily bolus or continuous infusion (C.I.) therapy. During this period, enhanced ex vivo agonist-induced platelet maximum aggregation (MA) was paralleled by an increase in plasma levels of TXB2 and PF4 as measured by RIA and ELISA, respectively. Platelet-rich plasma (PRP) specimens from bolus IL-6-treated patients demonstrated an increased incorporation of actin-binding protein and myosin in the cytoskeletal core (triton insoluble residue) as shown by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) in comparison to control specimens. Similarly, the integrin glycoprotein IIIa (GPIIIa) was also observed to be retained into the cytoskeleton by immunoblot. A significant decrease in hypotonic shock response (HSR) was observed over 87 hr of treatment in IL-6 C.I. patients, whereas in IL-6 bolus patients, a significant increase in HSR occurred immediately after the bolus, which was followed by a significant decrease in HSR after 23 hr. These results suggest that IL-6 alters platelet function in vivo.
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PMID:Alterations in platelet function in patients receiving interleukin-6 as cytokine therapy. 868 24

Myosin light chain kinase (MLCK) is a key regulator of smooth muscle contraction. The most conspicuous form of regulation is achieved by phosphorylation of the myosin light chain, allowing myosin to interact with actin. This interaction is regulated by actin-binding proteins that modulate actin filaments. In this review Kazuhiro Kohama and colleagues consider MLCK as an actin-binding protein and attempt to shed light on the cross-talk between the different kinds of regulation of the actin-myosin interaction in smooth muscle. An understanding of these mechanisms will assist the development of compounds with therapeutic importance in muscular disorders.
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PMID:Myosin light chain kinase: an actin-binding protein that regulates an ATP-dependent interaction with myosin. 881 Aug 74

Morphological changes in the dendritic spines have been postulated to participate in the expression of synaptic plasticity. The cytoskeleton is likely to play a key role in regulating spine structure. Here we examine the molecular mechanisms responsible for the changes in spine morphology, focusing on drebrin, an actin-binding protein that is known to change the properties of actin filaments. We found that adult-type drebrin is localized in the dendritic spines of rat forebrain neurons, where it binds to the cytoskeleton. To identify the cytoskeletal proteins that associated with drebrin, we isolated drebrin-containing cytoskeletons using immunoprecipitation with a drebrin antibody. Drebrin, actin, myosin, and gelsolin were co-precipitated. We next examined the effect of drebrin on actomyosin interaction. In vitro, drebrin reduced the sliding velocity of actin filaments on immobilized myosin and inhibited the actin-activated ATPase activity of myosin. These results suggest that drebrin may modulate the actomyosin interaction within spines and may play a role in the structure-based plasticity of synapses.
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PMID:Modulatory role of drebrin on the cytoskeleton within dendritic spines in the rat cerebral cortex. 892 25

Upon platelet activation by a high shear stress (108 dyne/cm2), actin and actin-binding protein increased rapidly into the Triton-insoluble cytoskeleton, whereas the association of myosin increased gradually. The amounts of cytoskeleton-associated myosin depended on the extent of aggregation. Preceding the maximal aggregation and ATP secretion, the 20 kDa light chain of myosin (MLC) is rapidly phosphorylated to approx. 45% of 20 kDa MLC and is then dephosphorylated. Cytoskeletal association of myosin and phosphorylation of 20 kDa MLC was inhibited by OP-41483, a prostaglandin I2 analog, which inhibited the full aggregation response to shear stress. Exposure to high shear stress resulted in an increased association of myosin light chain kinase and protein phosphatase types 1 and 2A with the cytoskeleton, while the cytoskeletal association of protein kinase C was not evident. These results indicate that 20 kDa MLC phosphorylation is involved in shear stress-induced platelet activation, and that cytoskeletal association of protein phosphatases may regulate the phosphorylation level of cytoskeletal elements such as myosin together with myosin light chain kinase.
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PMID:Shear stress-induced myosin association with cytoskeleton and phosphorylation in human platelets. 907 28

To date, protrusion of pseudopodia has been considered to be primarily responsible for translocation of free-living amoebae and leukocytes of higher organisms. Although there is little question that the pseudopodium plays an important role, little attention has been given to the cortical structures that are responsible for cell-substratum anchorage in amoeboid movement. Here, we report on a new knobby foot-like structure in amoebae of a cellullar slime mold, Dictyostelium discoideum. These feet, each about 1 micron in diameter, appear transiently in multiple units at the base of certain pseudopodia where the amoeba contacts a partially deformable substrate. The feet were discovered, and their spatial and temporal behavior relative to pseudopodial anchorage and invasive locomotion were observed, by examining Dictyostelium amoebae using a DIC video microscope providing an 0.3 micron depth of field. Key evidence for the anchoring role of the knobby feet was obtained by investigating amoebae, flattened in a specially devised observation chamber, and attracted by chemotaxis towards 3',5' cyclic-adenosine monophosphate (cAMP). The cAMP was released by highly localized, pulsed UV-microbeam irradiation of caged cAMP. We show by indirect immunofluorescence that the knobby feet contain a high concentration of filamentous (F-) actin, myoB (a member of Dictyostelium myosin-I family), and alpha-actinin (an actin-binding protein). Interestingly, myoB exhibits a circular disposition around each foot. Neither myosin-II (conventional myosin) nor the 269 kD protein, which has been recently identified as a talin homologue of Dictyostelium [Kreitmeier et al., 1995: J. Cell Biol. 129:179-188], are concentrated at the feet. We propose that the knobby feet provide anchorage to the substratum needed by lamellipodia to exert projectile forces for invading narrow spaces or otherwise for a flattened amoeba to secure itself to the deformable substratum. Some forms of adhesion plaques in higher organisms such as "podosomes" or "invadopodia" may perform functions similar to the knobby feet, but appear to differ in life time, cytoskeletal organization and composition. We have named the knobby foot "eupodium."
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PMID:Amoeboid movement anchored by eupodia, new actin-rich knobby feet in Dictyostelium. 909 56


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