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 28,634 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The various manifestations of platelet activation are derived from a reorganization of components of the contractile and microtubular systems. The controversial initial stages of excitation-contraction coupling in platelets lead to the release of calcium from the dense tubular system, the morphological counterpart of the muscle sarcotubular closed vesicles. Calcium triggers the actin-myosin interaction and the developing force, possibly together with a local increase of the cation concentration, may cause the collapse of the microtubular ring and its reappearance in the forming long pseudopodia. Actin-myosin interaction is modulated by several factors among which tropomyosin-troponin, responsible for the calcium-sensitivity of contractile processes, and phosphorylation of one of the myosin light chains. Platelet actin is anchored to the membrane and its sliding towards the short myosin filaments may form the basis for platelet shape change. Platelet alpha-actinin and actin-binding protein are able to aggregate actin into an impressive gel. Therefore, the contractile proteins seem to have a double role in controlling the consistency of the cytoplasmic gel on the one hand, and the contractile manifestations related to motility on the other hand. One of the most important features of the 'contracted' platelet is the rigidity of the pseudopodia brought about by the 'gelification' of actin filaments and the presence of microtubules. A new model for clot contraction is proposed, based on the rigidity of the long spiky pseudopodia and on the motile properties of platelets. While migrating towards each other, the interlocking pseudopodia from different platelets adhere to the polymerizing fibrin, compressing the fibrin nets in their pathway. Since the anchoring of contractile fibers to membranes is crucial for the platelet contractile manifestations, the integrity of the membrane structure should be considered in the study of pathological aspects of platelet function.
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PMID:The contractile system of blood platelets and its function. 36 20

The vesiculation of kidney proximal tubule microvilli has been examined in tissue slices, isolated brush borders and isolated microvilli. Vesiculation could be induced in tissue slices by 2,4-dinitrophenol and anoxia. Cycloheximide and fluoride had no effect. In brush borders and microvilli, the vesiculation was found to be essentially temperature-dependent. Whilst an osmotic swelling could be produced by hypo-osmolar media, the temperature-dependent vesiculation could not be prevented in hyper-osmolar media. Of a wide variety of reagents tested, only glutaraldehyde, mercuric chloride and mersalyl were effective in arresting the vesiculation. Electron micrographs show that vesiculation involves a collapse of the internal structure of the microvillus. However, the collapse was not associated with depolymerization of the microvillus actin filaments. Rather it appeared to be due to the parting of cross-bridges between the membrane and the actin filaments. The nature of these cross-bridges is discussed: it is suggested that alpha-actinin possesses the characteristics for the cross-bridging protein and that vesiculation might be explained by the displacement of alpha-actinin by tropomyosin.
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PMID:A morphometric and biochemical investigation of the vesiculation of kidney microvilli. 82 62

The maintainance of the shape of cells is often due to their surface elasticity, which arises mainly from an actin-rich cytoplasmic cortex. On locomotion, phagocytosis or fission, however, these cells become partially fluid-like. The finding of proteins that can bind to actin and control the assembly of, or crosslink, actin filaments, and of intracellular messages that regulate the activities of some of these actin-binding proteins, indicates that such 'gel-sol' transformations result from the rearrangement of cortical actin-rich networks. Alternatively, on the basis of a study of the mechanical properties of mixtures of actin filaments and an Acanthamoeba actin-binding protein, alpha-actinin, it has been proposed that these transformations can be accounted for by rapid exchange of crosslinks between actin filaments: the cortical network would be solid when the deformation rate is greater than the rate of crosslink exchange, but would deform or 'creep' when deformation is slow enough to permit crosslinker molecules to rearrange. Here we report, however, that mixtures of actin filaments and actin-binding protein (ABP), an actin crosslinking protein of many higher eukaryotes, form gels rheologically equivalent to covalently crosslinked networks. These gels do not creep in response to applied stress on a time scale compatible with most cell-surface movements. These findings support a more complex and controlled mechanism underlying the dynamic mechanical properties of cortical cytoplasm, and can explain why cells do not collapse under the constant shear forces that often exist in tissues.
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PMID:Resemblance of actin-binding protein/actin gels to covalently crosslinked networks. 215 33

Microcystin-LR (MCLR) is a commonly encountered blue-green algal hepatotoxin and a known inhibitor of cellular protein phosphatase types 1 and 2A. The toxin causes alterations in, and redistribution of, intermediate filaments, microtubules, and actin microfilaments (MFs) in affected cells. In this study, the effect of MCLR on the sequence of alterations in MFs and actin-associated proteins (AAPs) of isolated hepatocytes was examined in an effort to determine whether morphologic changes induced in MFs by microcystins are a result of prior dislocation of AAPs. We studied the effects of MCLR exposure on alpha-actinin and talin, two AAPs that play a role in the orientation of the MFs. Primary hepatocytes were incubated with 10 microns MCLR for 0-64 min. The distribution of actin, alpha-actinin, and talin were examined using fluorescence microscopy. MCLR induced similar changes in the distribution of actin and the AAPs. Actin filament redistribution was first observed after 12 min of MCLR exposure, and was characterized by detachment of MFs from the cell periphery, followed by condensation at distinct focal points and progressive collapse into the interior of affected cells. Changes in alpha-actinin and talin distribution were first observed after 20 min of toxin exposure. The AAPs appeared to detach from focal contacts on the cytoplasmic surface of the plasma membrane, condense into cytoplasmic aggregates, and ultimately collapse into a juxtanuclear bundle. The results of this study indicate that, in hepatocytes exposed to MCLR, the collapse of actin MFs occurs prior to the dislocation of alpha-actinin and talin. Changes in these actin associated proteins are not likely to account for the initial changes in actin MFs.
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PMID:Effects of microcystin-LR on actin and the actin-associated proteins alpha-actinin and talin in hepatocytes. 861 2

Lysophosphatidic acid (LPA) is a potent lipid mediator with actions on many cell types. Morphological changes involving actin polymerization are mediated by at least two cognate G protein-coupled receptors, LPA(1)/EDG-2 or LPA(2)/EDG-4. Herein, we show that LPA can also induce actin depolymerization preceding actin polymerization within single TR mouse immortalized neuroblasts. Actin depolymerization resulted in immediate loss of membrane ruffling, whereas actin polymerization resulted in process retraction. Each pathway was found to be independent: depolymerization mediated by intracellular calcium mobilization, and alpha-actinin activity and polymerization mediated by the activation of the small Rho GTPase. alpha-Actinin-mediated depolymerization seems to be involved in growth cone collapse of primary neurons, indicating a physiological significance of LPA-induced actin depolymerization. Further evidence for dual regulation of actin rearrangement was found by heterologous retroviral transduction of either lpa(1) or lpa(2) in B103 cells that neither express LPA receptors nor respond to LPA, to confer both forms of LPA-induced actin rearrangements. These results suggest that diverging intracellular signals from a single type of LPA receptor could regulate actin depolymerization, as well as polymerization, within a single cell. This dual actin rearrangement may play a novel, important role in regulation of the neuronal morphology and motility during brain development.
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PMID:Dual regulation of actin rearrangement through lysophosphatidic acid receptor in neuroblast cell lines: actin depolymerization by Ca(2+)-alpha-actinin and polymerization by rho. 1218 39

ALP, CLP-36 and RIL form the ALP subfamily of PDZ-LIM proteins. ALP has been implicated in sarcomere function in muscle cells in association with alpha-actinin. The closely related CLP-36 is predominantly expressed in nonmuscle cells, where it localizes to actin stress fibers also in association with alpha-actinin. Here we have studied the expression and functions of RIL originally identified as a gene downregulated in H-ras-transformed cells. RIL was mostly expressed in nonmuscle epithelial cells with a pattern distinct from that of CLP-36. RIL protein was found to localize to actin stress fibers in nonmuscle cells similarly to CLP-36. However, RIL expression led to partially abnormal actin filaments showing thick irregular stress fibers not seen with CLP-36. Furthermore, live cell imaging demonstrated altered stress fiber dynamics with rapid formation of new fibers and frequent collapse of thick irregular fibers in EGFP-RIL-expressing cells. These effects may be mediated through the association of RIL with alpha-actinin, as RIL was found to associate with alpha-actinin via its PDZ domain, and RIL enhanced the ability of alpha-actinin to cosediment with actin filaments. These results implicate the RIL PDZ-LIM protein as a regulator of actin stress fiber turnover.
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PMID:The PDZ-LIM protein RIL modulates actin stress fiber turnover and enhances the association of alpha-actinin with F-actin. 1472 62

Ephedra, a herb reported to suppress appetite and stimulate the sympathetic nervous system as well as cardiac performance, has recently been related to several adverse events, including seizure, stroke, hypertension, myocardial infarction, and sudden death. Here, we describe the case of a 45-year-old woman who died of cardiovascular collapse while taking ephedra. Tissue analysis revealed non-specific degenerative alterations in the myocardium (lipofuscin accumulation, basophilic degeneration and vacuolation of myocytes, as well as myofibrillary loss), associated with myocyte apoptosis, caspase activation, and extensive cleavage of miofibrillary proteins alpha-actin, alpha-actinin, and cardiac troponin T. Healthcare professionals are therefore urged to warn their patients about the risk of serious adverse effects, which may follow ephedra intake.
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PMID:A case of fatal ephedra intake associated with lipofuscin accumulation, caspase activation and cleavage of myofibrillary proteins. 1605 66

Collapsing glomerulopathy (CG) represents a morphologic pattern of disease, characterized histologically by glomerular capillary collapse, severe podocyte injury, and glomerular epithelial cell proliferation, and clinically by marked proteinuria and renal insufficiency. CG has multiple etiologies; however, many questions remain about its pathogenesis. A new set of animal models of CG, characterized by absence of the normal podocyte cytoskeletal protein alpha-actinin-4, has potential to help us gain a greater understanding of cellular events involved in producing this pattern of disease.
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PMID:Collapsing glomerulopathy: many means to a similar end. 1830 47