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PubMed2000

Gelsolin in complex with phosphatidylinositol 4,5-bisphosphate inhibits caspase-3 and -9 to retard apoptotic progression.

Apoptosis, or programmed cell death, occurs because of the activation of a protease cascade amplification circuit that includes the critical effector caspase-3. Previously, we identified the widely expressed actin modulatory protein gelsolin as a prominent substrate of caspase-3 and demonstrated that the N-terminal gelsolin cleavage product promotes apoptosis. Here we show that phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 3, 4-bisphosphate in pure micelles or mixed vesicles prevent caspase-3 cleavage of gelsolin. Moreover, phosphatidylinositol 4, 5-bisphosphate-gelsolin strongly inhibits caspase-3 and -9 activity through the formation of a stable phosphatidylinositol 4, 5-bisphosphate-gelsolin-caspase complex. In addition, phosphatidylinositol 4,5-bisphosphate-gelsolin prevents apoptotic progression mediated by caspase-3 in a cell-free system, and phosphatidylinositol 4,5-bisphosphate-gelsolin-caspase-9 and phosphatidylinositol 4,5-bisphosphate-gelsolin-caspase-3 complexes form in mouse embryonic fibroblasts during apoptosis induction when stimulated with fibronectin, to delay cell death. The results suggest that gelsolin can act as both an effector and an inhibitor of caspase-3, the latter in concert with phosphatidylinositol 4, 5-bisphosphate, and other membrane phospholipids to regulate the onset and progression of apoptosis.

Animals↗
PubMed2000

Evidence for gelsolin as a corneal crystallin in zebrafish.

We have shown that gelsolin is one of the most prevalent water-soluble proteins in the transparent cornea of zebrafish. There are also significant amounts of actin. In contrast to actin, gelsolin is barely detectable in other eye tissues (iris, lens, and remaining eye) of the zebrafish. Gelsolin cDNA hybridized intensely in Northern blots to RNA from the cornea but not from the lens, brain, or headless body. The deduced zebrafish gelsolin is approximately 60% identical to mammalian cytosolic gelsolin and has the characteristic six segmental repeats as well as the binding sites for actin, calcium, and phosphatidylinositides. In situ hybridization tests showed that gelsolin mRNA is concentrated in the zebrafish corneal epithelium. The zebrafish corneal epithelium stains very weakly with rhodamine-phalloidin, indicating little F-actin in the cytoplasm. In contrast, the mouse corneal epithelium contains relatively little gelsolin and stains intensely with rhodamine-phalloidin, as does the zebrafish extraocular muscle. We propose, by analogy with the diverse crystallins of the eye lens and with the putative enzyme-crystallins (aldehyde dehydrogenase class 3 and other enzymes) of the mammalian cornea, that gelsolin and actin-gelsolin complexes act as water-soluble crystallins in the zebrafish cornea and contribute to its optical properties.

Amino Acid Sequence↗
PubMed2002

Tropomyosin and gelsolin cooperate in controlling the microfilament system.

Tropomyosin has been shown to cause annealing of gelsolin-capped actin filaments. Here we show that tropomyosin is highly efficient in transforming even the smallest gelsolin-actin complexes into long actin filaments. At low concentrations of tropomyosin, the effect of tropomyosin depends on the length of the actin oligomer, and the cooperative nature of the process is a direct indication that tropomyosin induces a conformational change in the gelsolin-actin complexes, altering the structure at the actin (+) end such that capping by gelsolin is abolished. At increased concentrations of tropomyosin, heterodimers, trimers, and tetramers are converted to actin filaments. In addition, evidence is presented demonstrating that gelsolin, once removed from the (+) end of the actin, can reassociate with the newly formed tropomyosin-decorated actin filaments. Interestingly, the binding of gelsolin to the tropomyosin-actin filament complexes saturates at 2 gelsolin molecules per 14 actin and 2 tropomyosins, i.e. two gelsolins per tropomyosin-regulatory unit along the filament. These observations support the view that both tropomyosin and gelsolin are likely to have important functions in addition to those proposed earlier.

Actin Cytoskeleton↗
PubMed1987

Gelsolin is expressed in early erythroid progenitor cells and negatively regulated during erythropoiesis.

We have identified an approximately 85-kD protein in chicken erythrocytes which is immunologically, structurally, and functionally related to the gelsolin found in many muscle and nonmuscle cell types. Cell fractionation reveals a Ca2+-dependent partitioning of gelsolin into the soluble cytoplasm and the membrane-associated cytoskeleton of differentiating or mature erythrocytes. Depending on either the presence of Ca2+ during cell lysis or on the preincubation of the intact cells with the Ca2+-ionophore A23187, up to 40% of the total cellular gelsolin is found associated with the membrane skeleton. Expression of gelsolin shows a strong negative regulation during erythroid differentiation. From quantitations of its steady-state molar ratio to actin, gelsolin is abundant in early progenitor cells as revealed from avian erythroblastosis virus- and S13 virus-transformed cells which are arrested at the colony forming unit erythroid (CFU-e) stage of erythroid development. In these cells, which have a rudimentary and unstable membrane skeleton, gelsolin remains quantitatively cytoplasmic, irrespective of the Ca2+ concentration. During chicken embryo development and maturation, the expression of gelsolin decreases by a factor of approximately 10(3) in erythroid cells. This down regulation is independent from that of actin, which is considerably less, and is observed also when S13-transformed erythroid progenitor cells are induced to differentiate under conditions where the actin content of these cells does not change. In mature erythrocytes of the adult the amount of gelsolin is low, and significantly less than required for potentially capping of all membrane-associated actin filaments. We suggest that the gelsolin in erythroid cells is involved in the assembly of the actin filaments present in the membrane skeleton, and that it may provide for a mechanism, by means of its severing action on actin filaments, to extend the meshwork of the spectrin-actin-based membrane skeleton in erythroid cells during erythropoiesis.

Actins↗
PubMed1989

Association of gelsolin with actin filaments and cell membranes of macrophages and platelets.

Recent evidence that polyphosphoinositides regulate the function of the actin-modulating protein gelsolin in vitro raises the possibility that gelsolin interacts with cell membranes. This paper reports ultrastructural immunohistochemical data revealing that gelsolin molecules localize with plasma and intracellular membranes, including rough endoplasmic reticulum, cortical vesicles and mitochondria of macrophages, and blood platelets. Anti-gelsolin gold also labeled the surface and interior of secondary lysosomes presumably representing plasma gelsolin ingested by these cells from the lung surface by endocytosis. Gelsolin molecules, visualized with colloidal gold in replicas of the cytoplasmic side of the substrate-adherent plasma membrane of mechanically unroofed and rapidly frozen and freeze-dried macrophages, associated with the ends of short actin filaments sitting on the cytoplasmic membrane surface. A generalized distribution of gelsolin molecules in thin sections of resting platelets rapidly became peripheral, and plasmalemma association increased following thrombin stimulation. At later times the distribution reverted to the cytoplasmic distribution of resting cells. These findings provide the first evidence for gelsolin binding to actin filament ends in cells and indicate that gelsolin functions in both cytoplasmic and membrane domains.

Actins↗
PubMed2003

Regulation of the formation of osteoclastic actin rings by proline-rich tyrosine kinase 2 interacting with gelsolin.

Osteoclast activation is important for bone remodeling and is altered in multiple bone disorders. This process requires cell adhesion and extensive actin cytoskeletal reorganization. Proline-rich tyrosine kinase 2 (PYK2), a major cell adhesion-activated tyrosine kinase in osteoclasts, plays an important role in regulating this event. The mechanisms by which PYK2 regulates actin cytoskeletal organization and osteoclastic activation remain largely unknown. In this paper, we provide evidence that PYK2 directly interacts with gelsolin, an actin binding, severing, and capping protein essential for osteoclastic actin cytoskeletal organization. The interaction is mediated via the focal adhesion-targeting domain of PYK2 and an LD motif in gelsolin's COOH terminus. PYK2 phosphorylates gelsolin at tyrosine residues and regulates gelsolin bioactivity, including decreasing gelsolin binding to actin monomer and increasing gelsolin binding to phosphatidylinositol lipids. In addition, PYK2 increases actin polymerization at the fibroblastic cell periphery. Finally, PYK2 interacts with gelsolin in osteoclasts, where PYK2 activation is required for the formation of actin rings. Together, our results suggest that PYK2 is a regulator of gelsolin, revealing a novel PYK2-gelsolin pathway in regulating actin cytoskeletal organization in multiple cells, including osteoclasts.

Actins↗
PubMed2005

Separate functions of gelsolin mediate sequential steps of collagen phagocytosis.

Collagen phagocytosis is a critical mediator of extracellular matrix remodeling. Whereas the binding step of collagen phagocytosis is facilitated by Ca2+-dependent, gelsolin-mediated severing of actin filaments, the regulation of the collagen internalization step is not defined. We determined here whether phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2] regulation of gelsolin is required for collagen internalization. In gelsolin null fibroblasts transfected with gelsolin severing mutants, actin severing and collagen binding were strongly impaired but internalization and actin monomer addition at collagen bead sites were much less affected. PI(4,5)P2 accumulated around collagen during internalization and was associated with gelsolin. Cell-permeable peptides mimicking the PI(4,5)P2 binding site of gelsolin blocked actin monomer addition, the association of gelsolin with actin at phagosomes, and collagen internalization but did not affect collagen binding. Collagen beads induced recruitment of type 1 gamma phosphatidylinositol phosphate kinase (PIPK1gamma661) to internalization sites. Dominant negative constructs and RNA interference demonstrated a requirement for catalytically active PIPK1gamma661 for collagen internalization. We conclude that separate functions of gelsolin mediate sequential stages of collagen phagocytosis: Ca2+-dependent actin severing facilitates collagen binding, whereas PI(4,5)P2-dependent regulation of gelsolin promotes the actin assembly required for internalization of collagen fibrils.

Actins↗
PubMed2002

Gelsolin-induced epithelial cell invasion is dependent on Ras-Rac signaling.

Gelsolin is a widely distributed actin binding protein involved in controlling cell morphology, motility, signaling and apoptosis. The role of gelsolin in tumor progression, however, remains poorly understood. Here we show that expression of green fluorescent protein (GFP)-tagged gelsolin in MDCK-AZ, MDCKtsSrc or HEK293T cells promotes invasion into collagen type I. In organ culture assays, MDCK cells expressing gelsolin-GFP invaded pre-cultured chick heart fragments. Gelsolin expression inhibited E-cadherin-mediated cell aggregation but did not disrupt the E-cadherin-catenin complex. Co-expression of dominant-negative Rac1N17, but not RhoAN19 or Cdc42N17, counteracted gelsolin-induced invasion, suggesting a requirement for Rac1 activity. Increased ARF6, PLD or PIP5K 1alpha activity canceled out gelsolin-induced invasion. Furthermore, we found that invasion induced by gelsolin is dependent on Ras activity, acting through the PI3K-Rac pathway via the Ras guanine nucleotide exchange factor Sos-1. These findings establish a connection between gelsolin and the Ras oncogenic signaling pathway.

ADP-Ribosylation Factor 6↗
PubMed2005

Involvement of gelsolin in cadmium-induced disruption of the mesangial cell cytoskeleton.

Cadmium (Cd2+) is known to cause a selective disruption of the filamentous actin cytoskeleton in the smooth muscle-like renal mesangial cell. We examined the effect of Cd2+ on the distribution of the actin-severing protein, gelsolin. Over 8 h, CdCl2 (10 microM) caused a progressive shift of gelsolin from a diffuse perinuclear and cytoplasmic distribution to a pattern decorating F-actin filaments. Over this time filaments were decreased in number in many cells, and membrane ruffling was initiated. Western blotting and 125I-F-actin gel overlays demonstrated an increase in actin-binding gelsolin activity in the cytoskeletal fraction of cell extracts following Cd2+ treatment. In in vitro polymerization assays, gelsolin acted as a nucleating factor and increased the rate of polymerization. Cytosolic extracts also increased the polymerization rate. Addition of Cd2+ together with gelsolin further increased the rate of polymerization. Gelsolin enhanced depolymerization of purified actin, and Cd2+ partially suppressed this effect. However, cytoskeletal extracts from Cd2+-treated cells also markedly increased depolymerization, suggesting further that Cd2+ may activate cellular component(s) such as gelsolin for actin binding. We conclude that a major effect of Cd2+ on the mesangial cell cytoskeleton is manifest through activating the association of gelsolin with actin, with gelsolin's severing properties predominating under conditions found in Cd2+-treated cells.

Animals↗
PubMed1999

Regulation of neural differentiation by normal and mutant (G654A, amyloidogenic) gelsolin.

Gelsolin belongs to a family of proteins that modulate the structural dynamics of cytoskeletal actin. Gelsolin activity is required for the redistribution of actin occurring during membrane ruffling, cell crawling, and platelet activation. A point mutation (G654A) in the gelsolin gene causes a dominantly inherited systemic amyloidosis called familial amyloidosis of the Finnish type (FAF). This disease is characterized by a cranial neuropathy that cannot be explained solely by amyloid deposits. To address the question of whether gelsolin has a specific role in neural cell development, we transfected cDNA for wild type and G654A point-mutated gelsolin into a neural cell line, Paju, which can be induced to differentiate by treatment with phorbol 12-myristate 13-acetate. Overexpressed wild type gelsolin inhibited neural differentiation whereas mutated gelsolin did not, indicating that appropriate gelsolin activity is essential for neural sprouting. The G654A mutant gelsolin induced stabilization of F-actin and reduced the plasticity of neural development. This provides a novel etiopathogenetic mechanism for the neuronal dysfunction in FAF.

Adolescent↗
PubMed1999

Plasma gelsolin is reduced in trauma patients.

Tissue injury results in the release of the intracellular protein actin which is cleared from the circulation by the plasma proteins gelsolin and Gc-globulin, constituting the Extracellular Actin Scavenger System (EASS). Experimental studies have shown that excessive amounts of actin in the circulation can lead to a condition resembling multiple organ dysfunction syndrome (MODS), and we have previously demonstrated that the level of Gc-globulin is decreased after severe trauma. The purpose of the present study was to determine whether the plasma levels of gelsolin were altered in the early phase after trauma. Twenty-three consecutive trauma patients were studied. Plasma samples were assayed for gelsolin by immunonephelometry with polyclonal rabbit antihuman gelsolin prepared in our own laboratory. The median time from injury until the time the first blood sample was taken was 52 min (range 20-110) and the median Injury Severity Score (ISS) was 20 (range 4-50). The gelsolin level on admission was reduced significantly in the trauma patients compared with normal controls. The median level was 51 mg/L (7-967) vs. 207 mg/L (151-621), P < 0.0001. There was no correlation between admission levels of gelsolin and ISS or survival. This study illustrates that the plasma concentration of gelsolin is significantly diminished immediately after traumatic injury. Further studies are necessary to establish a role for gelsolin or EASS in the development of MODS in trauma patients. The level of serum or plasma gelsolin can be determined rapidly and accurately using a nephelometric assay.

Adult↗
PubMed1990

Modulation of gelsolin content in rat aortic smooth muscle cells during development, experimental intimal thickening and culture. An immunohistochemical and biochemical study.

Gelsolin is a Ca2+ and polyphosphoinositol-phospholipid regulated modulator of actin polymerization present in most mammalian cells and in plasma. Cytoplasmic gelsolin was first described in highly motile cells such as leukocytes, where actin polymerization is dynamic; however arterial smooth muscle cells (SMC), despite their stabilized actin bundles, express high levels of gelsolin. We have investigated gelsolin modulation in rat aortic SMC by immunohistochemistry, Western blotting and Northern hybridization using three models which are known to show modulation of actin isoform expression: development, aortic intimal thickening after experimental endothelial injury, and growth in culture. When related to the protein and mRNA content of adult aortic SMC, gelsolin is expressed about 50% in aortic SMC of five-day-old rats, 20-30% in SMC of intimal thickening 15 days after endothelial injury (when SMC are actively replicating) and in SMC growing in culture; in intimal thickening 60 days after injury (when SMC have returned to quiescence), the gelsolin content becomes similar to that of control SMC. The high level of gelsolin in smooth muscle (SM) tissues and the down regulation with proliferation and migration raises the question as to whether gelsolin in these cells has functions other than the dynamic control of actin filament length. The similar modulation patterns of gelsolin and alpha-SM actin suggest a preferential interaction between these two proteins.

Aging↗
PubMed2003

Recombinant plasma gelsolin infusion attenuates burn-induced pulmonary microvascular dysfunction.

Reduced plasma concentrations of the extracellular actin-binding proteins gelsolin and Gc-globulin correlate with pulmonary failure and death in humans after injury. The purpose of this study was to investigate the role of plasma gelsolin in the pathophysiology of inflammation-induced lung injury. We postulated that plasma gelsolin levels decrease at an early time point after burn injury and that the intravenous infusion of gelsolin prevents burn-induced pulmonary microvascular dysfunction. Adult Sprague-Dawley rats were randomized to undergo a 40% body surface area thermal injury (Burn) or manipulation without burn (Sham). Plasma gelsolin and Gc-globulin concentrations were determined at various times during the first 6 days of injury by Western blotting. Other animals were randomized to receive either recombinant human gelsolin (0.078, 0.78, or 7.8 mg) or albumin (7.8 mg) before and 8 h after Burn or Sham. Twenty-four hours later, pulmonary microvascular permeability was assessed by measuring the capillary filtration by use of an isolated, perfused lung model. We found that plasma gelsolin levels of burn-injured rats decreased to 10% of normal levels within 12 h and remained below normal levels for up to 6 days postinjury. Gc-globulin values also fall, but to a lesser extent and only transiently. Treatment of burned animals with intravenous infusions of recombinant human gelsolin prevented the increase in pulmonary microvascular permeability that accompanies this injury. Our findings are consistent with the hypothesis that plasma gelsolin depletion contributes to the pathophysiology of pulmonary microvascular dysfunction during inflammation.

Animals↗
PubMed1985

Gelsolin, a Ca2+-dependent actin-binding protein in a hamster insulin-secreting cell line.

Using a gel overlay technique we have previously described a 90,000-mol wt actin-binding protein in a number of hormone-secreting tissues and tentatively identified this protein as gelsolin. Gelsolin is a protein that cuts or solates cross-linked actin filaments and can also serve as a nucleating site for actin polymerization. The objective of this study was to isolate this protein from a hamster insulin-secreting (HIT) cell line and compare the immunologic properties and peptide maps of purified rabbit macrophage gelsolin, human platelet gelsolin, and the HIT cell 90,000-mol wt protein. DNase I-Sepharose retained the HIT cell actin-binding proteins in 1 mM CaCl2; some of the 90,000-mol wt protein could then be eluted with 1 mM EGTA. The remaining actin-binding proteins were eluted using a buffer containing SDS. The EGTA peak fractions contained two major protein bands of Mr = 90,000 and 42,000, which suggested that a 90,000-mol wt-actin complex was eluted from the DNase I-Sepharose column. Specific antibodies to the human platelet and rabbit macrophage gelsolins bound to the 90,000-mol wt bands in the eluates, but did not crossreact with other actin-binding proteins. Indirect immunofluorescence using an anti-human platelet gelsolin antibody localized the 90,000-mol wt protein to stress fibers that were also stained with phalloidin, which suggested that gelsolin is associated with actin in vivo. Tryptic peptide maps of all three radioiodinated gelsolins were virtually indistinguishable. Thus, gelsolin is a highly conserved gene product found in at least three diverse cell types, an insulin-secreting beta cell line, macrophages, and platelets, and may link a transient increase in Ca2+ cellular levels with changes in actin polymerization and/or the gel-sol state of these cells.

Animals↗
PubMed1992

Gelsolin binds to polymeric actin at a low rate.

Association of gelsolin with actin filament subunits was investigated by the decrease of the fluorescence intensity of a 7-nitro-2-oxa-1,3-diazole (NBD) label covalently linked to gelsolin. The rate constant of this reaction was found to be 4 x 10(3) M-1 s-1. Binding of NBD-labeled gelsolin to monomeric actin proceeds at a similar low rate. The rate of association of gelsolin that was unmodified to actin filament subunits was estimated too. Unmodified gelsolin was added to a mixture of actin filaments and actin-DNase I complex. The fractions of gelsolin that bound to actin filament subunits or to actin-DNase I complex depended on the relative rates of these two competing reactions. In this way it was possible to estimate the rate constant of association of unmodified gelsolin with actin filament subunits (2 x 10(4) M-1 s-1). Thus, gelsolin associates with actin filament subunits at a rate that is considerably slower than diffusion-controlled and similar to the rate of binding of gelsolin to monomeric actin.

Actins↗
PubMed1989

Differential modulation of actin-severing activity of gelsolin by multiple isoforms of cultured rat cell tropomyosin. Potentiation of protective ability of tropomyosins by 83-kDa nonmuscle caldesmon.

Multiple isoforms of tropomyosin (TM) of rat cultured cells show differential effects on actin-severing activity of gelsolin. Flow birefringence measurements have revealed that tropomyosin isoforms with high Mr values (high Mr TMs) partially protect actin filaments from fragmentation by gelsolin, while tropomyosins with low Mr values (low Mr TMs) have no significant protection even when the actin filaments have been fully saturated with low Mr TMs. We have also examined effect of nonmuscle caldesmon on the severing activity of gelsolin because 83-kDa nonmuscle caldesmon stimulates actin binding of rat cell TMs (Yamashiro-Matsumura, S., and Matsumura, F. (1988) J. Cell Biol. 106, 1973-1983). While nonmuscle caldesmon alone or low Mr TMs alone show no significant protection against fragmentation by gelsolin, the low Mr TMs coupled with 83-kDa protein are able to protect actin filaments. Further, high Mr TMs together with 83-kDa protein appear to block the severing activity completely. Electron microscopic analyses of length distribution of actin filaments have confirmed the results. The average length of control actin filaments is measured as 1.46 +/- microns, and gelsolin shortens the average length to 0.084 +/- 0.039 micron. Similar short average lengths are obtained when gelsolin severs actin complexed with low Mr TMs (0.080 +/- 0.045 micron) or with nonmuscle caldesmon (0.11 +/- 0.072 micron) while longer average length (0.22 +/- 0.18 micron) is measured in the presence of high Mr TMs. The simultaneous addition of nonmuscle caldesmon makes the average length considerably longer, i.e. 0.61 +/- 0.37 micron in the presence of low Mr TMs and 1.57 +/- 0.97 micron in the presence of high Mr TMs. Furthermore, the actin binding of gelsolin is strongly inhibited by co-addition of high Mr TMs and nonmuscle caldesmon. These results suggest that TM and gelsolin share the same binding site on actin molecules and that the differences in the actin affinities between TMs are related to their abilities of protection against gelsolin.

Actin Cytoskeleton↗
PubMed1985

Interaction of plasma gelsolin with G-actin and F-actin in the presence and absence of calcium ions.

Plasma gelsolin formed a very tight 1:2 complex with G-actin in the presence of Ca2+, but no interaction between gelsolin and G-actin was detected in the presence of excess EGTA. However, the 1:2 complex dissociated into a 1:1 gelsolin:actin complex and monomeric actin when excess EGTA was added. Plasma gelsolin bound tightly to the barbed ends of actin filaments and also severed filaments in the presence of Ca2+ and bound weakly to the filament barbed end in the presence of EGTA. The 1:2 gelsolin-actin complex bound to the barbed ends of filaments but did not sever them. By blocking the barbed end of filaments with plasma gelsolin, we determined the critical concentration at the pointed end in 1 mM MgCl2 and 0.2 mM ATP to be 4 microM. The dissociation rate constant for ADP-G-actin from the pointed end was estimated to be about 0.4 s-1 and the association rate constant to be about 5 X 10(4) M-1 s-1. Finally, we obtained evidence that plasma gelsolin accelerates but does not bypass the nucleation step and, therefore, that the concentration of gelsolin does not directly determine the concentration of filaments polymerized in its presence. Thus, gelsolin-capped filaments may not provide an absolutely reliable method for determining the rate constant for the association of ATP-G-actin at the pointed ends of filaments, but a reasonable estimate would be 1 X 10(5) M-1 s-1 in 1 mM MgCl2 and 0.2 mM ATP.

Actins↗
PubMed1994

Immunocytochemical localization of gelsolin in fibroblasts, myogenic cells, and isolated myofibrils.

Gelsolin was localized by immunofluorescence in fibroblasts and skeletal muscle cells using antibodies which eliminated the risk of detecting xenogenic plasma gelsolin. Gelsolin was consistently found to be closely associated with the elements of the microfilament system: In fibroblasts, a preferential labeling of the stress fibers was observed, whereas with myogenic cells and myofibrils isolated from skeletal muscle, a specific staining of the I-Z-I region in the sarcomeres was found. From double labeling of gelsolin and actin it became evident that the staining patterns for both proteins were practically coincident: The width and location of the fluorescent bands varied with the degree of contraction of the myofibrils. The region of cross-bridges in the A-zone, where thick and thin filaments overlap, remained unstained. The gelsolin staining of myofibrils was EGTA-resistant; it persisted after glycerol extraction and extensive washing. The presence of gelsolin in myofibrils after this treatment was also confirmed by immunoblotting. From these observations it was concluded that a significant part of the total gelsolin in skeletal muscle cells is tightly associated with the thin filaments, and is an integral part of the myofibrils even at low Ca(++)-concentrations. From the coincidence of actin and gelsolin staining in myofibrils it was concluded that gelsolin is localized along the whole length of the thin filaments in the sarcomere.(ABSTRACT TRUNCATED AT 250 WORDS)

Actin Cytoskeleton↗