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At least 973 records · Page 54Linked to original sources
PubMed1994

The failure to reconstitute the second extracellular matrix-integrin-cytoskeleton system in human endothelial cells on type V collagen.

We examined the formation of F-actin filaments and the expression of beta 1 integrin in human vascular endothelial cells cultured on type V collagen. The cells attached to the exogenous substrate, formed complete F-actin filaments, and expressed vinculin and beta 1 integrin 0.5-1 h after inoculation. These phenomena are referred to as the first ECM-integrin-cytoskeleton system. After 3-6 h, disassembly of the F-actin filaments was observed to occur from the leading edges, and the cells developed focal adhesions only in their central regions. After 12-24 h, the cells on the type V collagen failed to form the second ECM-integrin-cytoskeleton system, and gradually detached from the substrate. In contrast, the cells on type I collagen developed both the first and second system, and acclimatized themselves to the environment. Thrombospondin (TSP), an anti-adhesive protein, was capable of inhibiting the spreading of the cells both after 1 h and 24 h. However, type V collagen treated with TSP inhibited the cell spreading after 1 h, but not after 24 h. The attachment and spreading of the cells on type V collagen were little affected by an anti-TSP antibody and the synthetic peptide GRGDSP (Gly-Arg-Gly-Asp-Ser-Pro), which significantly inhibited the attachment and spreading of the cells on TSP. Taken together, these results suggest that the cell detachment from type V collagen is not attributed to endogenously produced TSP (or member of TSP family) with anti-adhesive properties, but resulted from the failure to reconstitute the second ECM-integrin-cytoskeleton system in focal adhesion.

Actins↗
PubMed1995

The postsynaptic localization of the glycine receptor-associated protein gephyrin is regulated by the cytoskeleton.

The mechanisms underlying the postsynaptic localization of neurotransmitter receptors are poorly understood. Recently, the peripheral membrane protein gephyrin has been shown to be essential for the formation of inhibitory glycine receptor clusters in cultured rat spinal cord neurons. In vitro gephyrin binds with high affinity to polymerized tubulin. Here, the interaction of gephyrin with different components of the cytoskeleton was investigated in primary cultures of rat spinal neurons. After treatment with alkaloids affecting the cytoskeleton, the morphology of post-synaptic gephyrin clusters was analyzed by confocal immunofluorescence microscopy. Depolymerization of microtubules by demecolcine reduced both the percentage of cells with postsynaptic gephyrin clusters and the number of clusters/cell. The size of the remaining gephyrin clusters was increased whereas their gephyrin density was significantly lower than under control conditions. Depolymerization of microfilaments by cytochalasin D in contrast generated smaller clusters of increased gephyrin density. Demecolcine also dispersed postsynaptic glycine receptor clusters as revealed by immunostaining with a specific monoclonal antibody. These findings support the view that in vivo gephyrin anchors receptor polypeptides to the cytoskeleton by a complex interaction with microtubules and microfilaments.

Alkaloids↗
PubMed1994

Translocation of p72syk to the cytoskeleton in thrombin-stimulated platelets.

Thrombin stimulation induces a dramatic increase in the activity of p72syk in platelets. We have found that activated p72syk, which is phosphorylated on tyrosine residue(s), translocates from the Triton X-100-soluble fraction to the Triton X-100-insoluble, cytoskeleton-rich fraction after thrombin stimulation. In addition, the redistribution of p72syk from the 100,000 x g Triton X-soluble fraction and the membrane skeleton was found to correlate with an increased level of p72syk in the cytoskeleton. Furthermore, the early phase of p72syk translocation (within 60 s) was significantly inhibited with cytochalasin D, whereas the late phase of p72syk translocation (after 90 s) was completely inhibited with RGDS tetrapeptide treatment. These results suggest that translocation of the activated p72syk to the cytoskeleton correlates with different phases of the platelet activation process through actin polymerization and glycoprotein IIb/IIIa-fibrinogen-mediated aggregation of platelets and, hence, may have a regulatory role in tyrosine phosphorylation of platelets.

Animals↗
PubMed1994

[Features of filamentous cytoskeletons in acquired multidrug-resistance of HL-60 human leukemia cell line].

Acquired resistance to chemotherapeutic drugs by tumor cells is an important obstacle to effective therapy of human malignancy. These resistance cell lines originated from human or rodent have been characterized by increased expression of MDR (Multidrug-resistance) gene and P-glycoprotein which plays as efflux pump of drugs from cells. These multidrug-resistance sublines also have been reported increased activities of protein kinases and glutathione S-transferase-pi. Although there have been extensive biophysical and biochemical characterization of the differences between parental lines and MDR tumor cell sublines, morphologic observations have been limited. In this study, filamentous cytoskeletons which involve many biological phenomena such as maintenance of cell morphology, mitosis, cellular movement, transport, and adhesion, were observed by confocal laser microscopy. To compare the expression of each cytoskeletons, fluorescent intensities of cells stained for each cytoskeletons were measured by confocal laser microscopic system. Utilizing this methodology, higher microtubular expression was observed in HL-60/ADR and K562/ADR than in their parental lines, but no significant differences of actin and vimentin were observed. Phosphorylation by protein kinases has been established as a key factor in the regulation of cytoskeletal function. But little is known about the role of protein phosphorylation in cytoskeletal function. Since increased activities of PKC and PTK were detected in HL-60/ADR, the effect of PKC inhibitor, staurosporine (STR), or PTK inhibitor, genistein (GNS), on cell growth was detected. STR and GNS reduced the resistance to Adriamycin in HL-60/ADR. Furthermore, STR and GNS disrupted the filamentous structure of microtubules in HL-60/ADR, and suppressed the expression of microtubules to 37%, and 49%, respectively. In contrast, PKC activator, phorbol ester (TPA), caused stronger microtubular assembling in HL-60/ADR, and increased the expression of microtubules to 134%. Resulting from this study, it is likely that acquired MDR of HL-60 and K562 was associated with increased expression of microtubules, and microtubular assembling or disassembling was considered to be regulated in part by PKC and PTK.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1994

Microtubule cytoskeleton in hyphal growth. Response to nocodazole in a sensitive and a tolerant strain of the homobasidiomycete Schizophyllum commune.

In the wild-type strains of the homobasidiomycete Schizophyllum commune microtubules were totally depolymerized by low concentrations of nocodazole, while high concentrations of benomyl only modified the structure of microtubule cytoskeleton. In the nocodazole-tolerant mutant strain NT30 the microtubule cytoskeleton remained partly functional at a nocodazole concentration which demolished the microtubules in the wild-type strains. The continuation of apical growth for several hours in the wild-type strain without cytoplasmic microtubules indicated that microtubules are not the major elements in hyphal extension growth. However, the irregular branching of the treated apical cells both in the nocodazole-sensitive and -tolerant strain suggested that an intact microtubule cytoskeleton is needed for maintaining the direct extension of the leading hyphae at the colony edge. In the nocodazole-sensitive strain growth in the absence of polymerized microtubules frequently led to the death of the apical cells even when the drug was removed. In the tolerant strain the nuclear divisions continued in spite of nocodazole, but the uninucleate hyphal compartments became multinucleate. This probably resulted from poor segregation of nuclei and septation of hyphae at telophase, which indicated that these processes might be dependent on proper polymerization of cytoplasmic microtubules in higher fungi. The different electrophoretic mobility of the beta-tubulin from the NT30 strain and its parental strains suggested that the tolerance of the NT30 to nocodazole could be due to a mutation in a beta-tubulin encoding gene.

Benomyl↗
PubMed1994

The actin cytoskeleton is important for the stimulation of cholesterol esterification by atherogenic lipoproteins in macrophages.

Stimulation of intracellular cholesterol esterification, which is catalyzed by the enzyme acyl-coenzyme A: cholesterol O-acyltransferase (ACAT), by atherogenic lipoproteins in macrophages is a key step in the ability of these cells to store lipoprotein-cholesterol and in the eventual development of atheroma foam cells. Herein, we provide evidence that the actin cytoskeleton plays an important role in the stimulation of cholesterol esterification by atherogenic lipoproteins in macrophages. When the actin cytoskeleton of cultured mouse peritoneal macrophages was disrupted by treatment with cytochalasin D or Clostridial C2 toxin, the ability of beta very low density lipoprotein (beta-VLDL) to stimulate cholesterol esterification was decreased 3-6-fold, even under conditions in which beta-VLDL protein degradation, cholesteryl ester hydrolysis, or net cholesterol delivery to the cells was matched. Esterification of cellular phospholipids and triglycerides was not affected by this treatment. Cytochalasin D treatment of macrophages also inhibited the ability of acetyl-low density lipoprotein, another foam cell-forming lipoprotein, to stimulate cholesterol esterification, but stimulation of cholesterol esterification by 25-hydroxycholesterol was not inhibited by cytochalasin D. Cytochalasin D was found to inhibit neither the exit of beta-VLDL-derived cholesterol from lysosomes nor the ability of beta-VLDL to down-regulate endogenous cholesterol synthesis. From these data we conclude that an intact actin cytoskeleton is necessary for efficient stimulation of cholesterol esterification by atherogenic lipoproteins in macrophages. Although the exact function of actin in the cholesterol esterification pathway remains to be determined, our data rule out a general role for actin in intracellular cholesterol trafficking or maintenance of ACAT enzyme activity. Rather, we speculate that actin filaments play a role in specific cellular entry processes of atherogenic lipoproteins and/or in establishing transport or contact between the plasma membrane cholesterol substrate pool and the ACAT enzyme in macrophages.

Actins↗
PubMed1993

[Pathophysiology of cytoskeleton and extracellular matrix in failing myocardium].

Cytoskeleton of myocytes and extracellular matrix play an essential role for maintaining cellular function. Alterations in humoral factors observed in heart failure, e.g., excess of plasma norepinephrine and angiotensin II, injure the microtubule structure probably through Ca overload and increase the collagen synthesis of the cardiac fibroblast. Recent studies demonstrated that network structures of microtubules and intermediate filaments are disrupted in the myocardium obtained from patients with heart failure. Changes in cytoskeletons and extracellular matrix may affect the contractile function, since they organize the intra- and inter-cellular architectures. Pathophysiological roles of cytoskeletons and extracellular matrix in failing hearts deserve further studies.

Angiotensin II↗
PubMed1995

The effects of diethyldithiocarbamate (DDC) on the astrocytic cytoskeleton.

The dithiocarbamates are a group of compounds that are used extensively in industry, agriculture and medicine. Exposure to these compounds has caused deleterious effects to both the central and peripheral nervous systems. Cultured rat hippocampal astroglia treated with 35 micrograms/ml diethyldithiocarbamate (DDC) in media were studied for alterations to the cytoskeleton. Examination by both immunohistochemistry and scanning electron microscopy revealed disruption of the cytoskeletal elements. This occurred in a progressive time-dependent manner. Electrophoretic patterns demonstrated two cytoskeletal protein alterations. The microtubular protein, beta-tubulin, appeared to have an altered mobility while the major intermediate filament protein, glial fibrillary acidic protein (GFAP), was decreased. The cytoskeleton appears to be an important cellular target for injury by DDC exposure. This study has demonstrated that DDC induces alterations in the architecture of the cytoskeleton of astroglia and suggests that these changes involve microtubular and intermediate filament proteins.

Animals↗
PubMed1996

Fibrinogen binding to ICAM-1 on EA.hy 926 endothelial cells is dependent on an intact cytoskeleton.

Fibrinogen is a ligand for Intercellular Adhesion Molecule-1 (ICAM-1), and enhances monocyte-endothelial cell interaction by coupling Mac-1 on monocytes to ICAM-1 on endothelial cells. We investigated the role of the cytoskeleton in fibrinogen binding to the human endothelial cell line EA.hy 926 using immunofluorescence techniques. In this cell line TNF alpha induced the simultaneous appearance of stress fibers and of ICAM-1, which was clustered predominantly on endothelial cell projections. Incubation of TNF alpha-stimulated endothelial cells with fibrinogen resulted in binding of fibrinogen to ICAM-1 on these cell projections. Disruption of the cytoskeleton by cytocholasin B abolished fibrinogen binding. Activation of protein kinase C with 12-O-tetradecanoyl phorbol-13-acetate resulted in simultaneous loss of both stress fibers and fibrinogen binding. These results suggest that a connection between ICAM-1 and the cytoskeleton results in clustering of ICAM-1 on cell projections, which is required for fibrinogen binding.

Cell Line↗
PubMed1996

Mechanisms of stimulation of the respiratory burst by TNF in nonadherent neutrophils: its independence of lipidic transmembrane signaling and dependence on protein tyrosine phosphorylation and cytoskeleton.

This study concerns the controversial problem of whether the TNF-alpha (TNF) induces a respiratory burst in human neutrophils in suspension. The results have shown that in these cells TNF induces a classical respiratory burst. In fact, the production of oxygen free radicals 1) is linked to the translocation of NADPH oxidase components from cytosol to the plasma membrane, 2) does not take place in neutrophils from a patient lacking the cytochrome b558, and 3) does not involve other sources such as mitochondrial respiratory chain or xanthine oxidase. Signal transduction studies have demonstrated that this respiratory burst 1) is not accompanied by calcium transients, stimulation of phosphoinositide turnover, and phospholipase D activity (moreover, this burst is associated with the stimulation of the activity of phospholipase A2, but not of sphingomyelinase); 2) is strictly dependent on activation of tyrosine kinases, which is functional to the translocation to the plasma membrane of the cytosolic NADPH oxidase component rac; and 3) is dependent on the integrity of the cytoskeleton because it is completely suppressed by cytochalasin B. The integrity of the cytoskeleton is required for a full translocation of all the NADPH oxidase components and for an optimal activation of tyrosine kinases, but not for phospholipase A2 activation. Taken together, these findings demonstrate that TNF activates the NADPH oxidase through stimulation of tyrosine kinases, whose function is cytoskeleton-dependent, and raise the problem of whether the activation of this respiratory burst involves signals arising from TNF-activated beta2 integrins.

Cell Separation↗
PubMed1996

Modulatory role of drebrin on the cytoskeleton within dendritic spines in the rat cerebral cortex.

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.

Actins↗
PubMed1997

Role of Rho protein in lovastatin-induced breakdown of actin cytoskeleton.

The Rho GTPases are involved in actin cytoskeleton organization and signal transduction. They need polyisoprenylation for membrane association and activation. Lovastatin, a hydroxymethylglutaryl coenzyme A inhibitor, prevents isoprene synthesis and thereby lipid modification of the Rho protein carboxy terminus. Because lovastatin causes rounding up of cultured cells, we investigated whether the compound acts on the actin cytoskeleton through Rho proteins. Lovastatin treatment decreased F-actin content in a time- and concentration-dependent manner. G-actin content remained unchanged. In lovastatin-treated NIH 3T3 cells, the amount of Rho protein which was ADP-ribosylated by Clostridium botulinum exoenzyme C3 decreased in membranes and increased in the cytosol fraction. Cycloheximide prevented lovastatin-induced rounding up of cells. However, after microinjection or direct application of exoenzyme C3, cells treated with cycloheximide and lovastatin rounded up again. On the contrary, lovastatin-treated, round Swiss 3T3 cells reverted to a flat morphology when microinjected with dominant active RhoA (Val14RhoA). Escherichia coli cytotoxic necrotizing factor (CNF1) which activates Rho proteins caused flattening of round, lovastatin-treated NIH 3T3 cells. These results suggest that lovastatin affects the actin cytoskeleton through inactivation of Rho proteins.

3T3 Cells↗
PubMed1998

Microtubule coils versus the surface membrane cytoskeleton in maintenance and restoration of platelet discoid shape.

The discoid form of blood platelets is important to their function in hemostasis. Recent studies have suggested that the spectrin-rich surface membrane cytoskeleton and the cytoplasmic, actin-rich cytoskeleton are responsible for discoid shape, shape change, and recovery after activation or chilling. Earlier studies had suggested that circumferential coils of microtubules supported the disc shape of resting platelets and that their repositioning or reassembly restored disc shape after exposure to low temperature. The present study has used the chilling-rewarming model, together with microtubule stabilizing (taxol) and disassembling (vincristine) agents to retest the relative importance of the surface membrane cytoskeleton and circumferential microtubules in platelet discoid shape and its restoration. Washed platelet samples were rested at 37 degrees C and chilled to 4 degrees C; chilled and rewarmed to 37 degrees C for 60 minutes; or chilled, rewarmed, and exposed to the same cycle in the presence or absence of vincristine or taxol and fixed for study by disseminated interference phase contrast microscopy and electron microscopy. Rhodamine-phalloidin and flow cytometry were used to measure changes in actin filament assembly. Chilling caused loss of disc shape, pseudopod extension, disassembly of microtubule coils, and assembly of new actin filaments. Rewarming resulted in restoration of disc shape, pseudopod retraction, disassembly of new actin filaments, and reassembly of circumferential microtubule coils. Vincristine converted discoid platelets to rounded cells that extended pseudopods when chilled and retracted them when rewarmed, leaving spheres that could undergo the same sequence of changes when chilled and rewarmed again. Taxol prevented cold-induced disassembly of microtubules and limited pseudopod formation. Rewarming caused retraction of pseudopods on taxol-treated, discoid cells. Cytochalasin B, an agent that blocks new actin filament assembly, alone or in combination with taxol, inhibited the cold-induced shape change but not dilation of the open canalicular system. Rewarming eliminated open canalicular system dilation and restored lentiform appearance. The results indicate that microtubule coils are the major structural elements responsible for disc shape and its restoration after submaximal stimulation or rewarming of chilled platelets.

Actins↗
PubMed1998

Desensitization of formyl peptide receptors is abolished in calcium ionophore-primed neutrophils: an association of the ligand-receptor complex to the cytoskeleton is not required for a rapid termination of the NADPH-oxidase response.

Binding of ligands to N-formyl peptide chemoattractant receptors exposed on human neutrophils generates signals in the cells that induce an activation of the superoxide anion producing NADPH-oxidase. Ligand binding is followed by a rapid association of the ligand-receptor complex with the cytoskeleton, a process leading to desensitization of the cells with respect to NADPH-oxidase activation. We show that neutrophils that have experienced an intracellular calcium rise obtained through interaction with the calcium-specific ionophore ionomycin are "primed" with respect to the FMLP-induced production of superoxide anions. Mobilization of FMLP receptors from intracellular pools is one well-known mechanism behind the primed response. Based on our finding that ionomycin-treated neutrophils could not be desensitized, we suggest that the lack of association between the ligand-receptor complex and the cytoskeleton is an additional priming mechanism. Since in vivo-exudated neutrophils, which also had mobilized intracellular organelles, could be desensitized, we suggest that the abolished desensitization in ionomycin-treated neutrophils is not due to an inability of newly recruited receptors to couple to the cytoskeleton. We show that a rapid termination of FMLP-induced superoxide anion production is obtained in both desensitizable and nondesensitizable neutrophils, suggesting that the desensitization phenomenon is of limited importance in the oxidase termination process.

Adult↗
PubMed1997

Effect of disruption of the cytoskeleton on smooth muscle contraction.

The relationship between passive tension applied to aortic rings and the resulting increase in tissue length was nearly linear over the range of 1 to 15 g. However, even with increasing tissue length, within the range of 1 to 10 g passive tension, the total active force generated upon stimulation was not significantly changed. These observations emphasize the great flexibility of the mechanism(s) underlying the contractile response of vascular smooth muscle with regard to changes in tissue preload and length. Neither the blockade of microtubule polymerization by colchicine nor the blockade of actin polymerization by cytochalasin B significantly changed the slope of the tissue length-preload curve, indicating no effect on the tissues' capacity to stretch at a given preload. With stimulation of the tissue at different levels of stretch, colchicine caused an increase in the initial fast component of active tension development, but partially blocked the secondary slow rise in tension. Cytochalasin B dramatically reduced the total contractile response at each preload studied, and this effect was confined almost exclusively to the secondary slow increase in tension. When tissues were cooled to cause complete dissolution of the microtubule network and then warmed in the presence of colchicine to prevent repolymerization of both the active and stable populations of microtubules, there was also a significant reduction in the slow component of contraction with no effect on the fast response. The partial blockade of synthesis of the microtubule-associated motor protein kinesin by application of an antisense oligonucleotide to aortae in situ or to aortic rings in tissue culture significantly reduced the contractile response to potassium depolarization. The results suggest that the microtubules and the actin filaments of the cytoskeleton play an active role in slow force development as opposed to a solely passive role based on the effect of the static, structural properties of these filaments on mechanical resistance. We propose that a tension-bearing element of the actin-containing cytoskeleton undergoes remodeling to adjust tension within the system. The microtubules could act either through the directed movement of the molecules involved in the transduction process or through the direct action of kinesin-mediated intracytoskeletal interactions in force development that involve a remodeling of the tension-bearing elements of the cytoskeleton.

Animals↗
PubMed1998

[Association of phosphoinositide-specific phospholipase Cgamma1 with elements of cytoskeleton in A-431 cells].

It is shown that phosphoinositide-specific phospholipase C gamma 1 (PLC gamma 1), a substrate of growth factor receptors, is associated with cytoskeleton in A-431 cells. PLC gamma 1 is co-localized only with the cortical actin but not with actin stress fibers. Since EGF receptor is also co-localized with the cortical actin it is concluded that PLC gamma 1 co-localized with actin is mediated by the EGF receptor. After the treatment with cytochalasin B PLC gamma 1 is co-localized with actin aggregates and cytoskeleton elements other than actin. Using double immunofluorescence PLC gamma 1 is shown to be associated with cytokeratin intermediate filaments. The cross-talking of different cytoskeleton elements and their participation in cell signaling is discussed.

Actins↗
PubMed1998

Cytoskeleton and mitochondrial morphology and function.

It has been well established that the cytoskeleton is an essential modulator of cell morphology and motility, intracytoplasmic transport and mitosis, however cytoskeletal linkage to the organelles has not been unequivocally demonstrated. Indeed, cytoskeleton appears to be essential in determining and modulating gene phenotype as a function of cellular environment. According to recent studies, the organization of the cytoskeleton network together with associated protein(s) could be essential in regulating mitochondrial function and particularly the permeability of the mitochondrial outer membrane to ADP. The aim of this chapter is to summarize the main properties of the cytoskeletal environment of mitochondria and the possible role(s) of this network in mitochondrial function in myocytes.

Adenosine Diphosphate↗
PubMed1999

Role of the actin cytoskeleton in insulin action.

Insulin has diverse effects on cells, including stimulation of glucose transport, gene expression, and alterations of cell morphology. The hormone mediates these effects by activation of signaling pathways which utilize, 1) adaptor molecules such as the insulin receptor substrates (IRS), the Src and collagen homologs (Shc), and the growth factor receptor binding protein 2 (Grb2); 2) lipid kinases such as phosphatidylinositol 3-kinase (PI 3-Kinase); 3) small G proteins; and 4) serine, threonine, and tyrosine kinases. The activation of such signaling molecules by insulin is now well established, but we do not yet fully understand the mechanisms integrating these seemingly diverse pathways. Here, we discuss the involvement of the actin cytoskeleton in the propagation and regulation of insulin signals. In muscle cells in culture, insulin induces a rapid actin filament reorganization that coincides with plasma membrane ruffling and intense accumulation of pinocytotic vesicles. Initiation of these effects of insulin requires an intact actin cytoskeleton and activation of PI 3-kinase. We observed recruitment PI 3-kinase subunits and glucose transporter proteins to regions of reorganized actin. In both muscle and adipose cells, actin disassembly inhibited early insulin-induced events such as recruitment of glucose transporters to the cell surface and enhanced glucose transport. Additionally, actin disassembly inhibited more prolonged effects of insulin, including DNA synthesis and expression of immediate early genes such as c-fos. Intact actin filaments appear to be essential for mediation of early events such as association of Shc with Grb2 in response to insulin, which leads to stimulation of gene expression. Preliminary observations support a role for focal adhesion signaling complexes in insulin action. These observations suggest that the actin cytoskeleton facilitates propagation of the morphological, metabolic, and nuclear effects of insulin by regulating proper subcellular distribution of signaling molecules that participate in the insulin signaling pathway.

Actins↗