Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Spectrin”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 487 records · Page 27Linked to original sources
PubMed1993

Cloning of a portion of the chromosomal gene and cDNA for human beta-fodrin, the nonerythroid form of beta-spectrin.

A 96-bp synthetic oligonucleotide corresponding to an amino acid sequence near the N-terminus of erythroid beta-spectrin was used to screen a human genomic library, and two overlapping recombinants were isolated. DNA sequence analysis established that the genomic fragment encoded beta-fodrin, the nonerythroid form of beta-spectrin, by correlation to a known amino acid sequence of human brain beta-fodrin. The genomic DNA contained regions that cross-hybridized with an erythroid beta-spectrin cDNA probe, and the DNA sequence of these regions revealed a high degree of identity with that of erythroid beta-spectrin and a similar exon/intron organization. A single-copy DNA fragment of the beta-fodrin genomic clone was used to screen a lymphoid cell cDNA library and two recombinants were isolated. The composite DNA sequence of these various genomic and cDNA clones encoded almost all of the first twelve 106 amino acid repeat segments of beta-fodrin that shared 58% identity and 75.5% similarity with the amino acid sequence of beta-spectrin and 66% identity with the nucleotide sequence of beta-spectrin cDNA. The chromosomal localization of the gene was determined to be chromosome 2 by hybridization of a single-copy probe derived from the cloned genomic DNA to DNA of a panel of somatic hybrid cell lines, and in situ hybridization localized the gene to band 2p21. beta-Fodrin was assigned the gene symbol SPTBN1.

Amino Acid Sequence↗
PubMed1995

A TaqI polymorphism in the human erythroid beta spectrin gene.

Human erythroid spectrin consists of an alpha beta heterodimer. Abnormalities of spectrin are a common cause of hereditary haemolytic anaemias such as hereditary elliptocytosis (HE) and hereditary spherocytosis (HS). To identify the spectrin gene mutation one needs initially to establish which of the spectrin subunits is defective. For this purpose, the beta spectrin restriction fragment length polymorphism (RFLP) we describe here will be useful in linkage analysis. The elucidation of an Ala-->Gly beta spectrin gene mutation in a family with HE, highlights the importance of this TaqI polymorphism in establishing linkage.

Alanine↗
PubMed1990

Alpha-spectrin immunoanalog in Acanthamoeba cells.

A monospecific, affinity purified antibody was prepared against chicken erythrocyte alpha-spectrin. The antibody cross-reacted with only one high molecular weight polypeptide (235 kDa) from whole Acanthamoeba cells. The localization of alpha-spectrin-related antigen in Acanthamoeba cells was examined using immunofluorescence and postembedding cytochemical techniques. Three patterns of distribution of alpha-spectrin immunoanalog were distinguished: as submembranous layer, cytoplasmic aggregates and uniform dispersion through the cytoplasm. Immunoelectron microscopic studies showed that the colloidal gold label was located in the cytoplasm in the vicinity of the plasma membrane. The gold particles were also aggregated around unidentified cytoplasmic filamentous structures. The presence of spectrin-related protein in protozoan cells of Acanthamoeba is in accordance with previous assumptions of the widespread occurrence of spectrin-related proteins. The heterogenous distribution of the immunoanalog of alpha-spectrin protein in Acanthamoeba cells is discussed.

Acanthamoeba↗
PubMed1989

Two distinct variants of erythrocyte spectrin beta IV domain.

We report two distinct variants affecting the beta IV domain of erythrocyte spectrin, designated spectrin Saint-Chamond and spectrin Tlemcen. They were discovered in a French family and an Algerian individual, respectively. They appeared clinically and morphologically asymptomatic in the heterozygous state. In two-dimensional maps of spectrin partial digests, both mutants were manifested by cathodic shifts (with no change of the molecular weights) of the peptides that cover the N-terminal region of spectrin beta IV domain. The relevance of the abnormal peptides to the beta IV domain was established by quantitative analysis and by Western blotting using anti-beta IV domain-specific antibodies. These two variants are thus far the most distal variants of spectrin to be defined on an unequivocal structural basis.

Adult↗
PubMed1995

Erythrocytes carrying mutations in spectrin and protein 4.1 show differing sensitivities to invasion by Plasmodium falciparum.

The role of the erythrocyte skeleton in the invasion process of Plasmodium falciparum was evaluated using genetically variant erythrocytes containing well-defined molecular defects in alpha spectrin (alpha Sp) or protein 4.1 from eight unrelated families. Invasion into red cells from subjects of three black families with hereditary pyropoikilocytosis (HPP) due to inheritance of alpha I/74 mutant spectrin was significantly reduced in cells both from the patients and from the relatives of these who carried asymptomatic hereditary elliptocytosis (HE). Likewise, reduced invasion was also seen in red cells from two families with HE in which the alpha I/65 variant spectrin was present. Resistance to invasion was not absolute in any sample and varied between 38% and 71% of that seen in normal cells. The decreased invasion correlated with the percentage of spectrin dimers present within the membrane of variant cells. In contrast, invasion into elliptocytes from three families that had a partial deficiency in protein 4.1 (HE/4.1+) but a normal percentage of spectrin dimers was either unchanged or increased. The precise mechanism and molecular basis behind the reduced invasion into HPP and HE red cells bearing Sp alpha I domain variants remains to be elucidated but might relate to alterations in merozoite/red cell-receptor interactions and/or merozoite endocytosis. The occurrence of elliptocytosis with spectrin defects (in particular, Sp alpha I/65 and Sp alpha I/46 variants in West Africa) suggests that these mutations of the alpha Sp gene could be related to some protection against malaria.

Anemia, Hemolytic, Congenital↗
PubMed2001

Juvenile-hormone-dependent interaction of actin and spectrin is crucial for polymorphic differentiation of the larval honey bee ovary.

Programmed cell death in the worker ovary of Apis mellifera reduces the number of ovarioles during metamorphosis from 150-200 primordia to less than 10. In contrast, practically all ovarioles in the ovary of queens survive to the adult stage. The correct formation and persistence of polyfusomes has been suggested as a critical factor for ovariole survival. We have analyzed the developmental dynamics of F-actin and alpha-spectrin in fusomes of queen and worker larvae, and in juvenile-hormone-treated worker larvae. Small fusomes containing actin and spectrin can be detected in the ovaries of fourth instar larvae in both castes. After molting to the fifth instar, the actin-spectrin association persists in the enlarged fusomes of queen ovarioles. In workers, actin dissociates from the fusomal and cortical alpha-spectrin. Coinciding with the appearance of apoptosis markers, large agglomerates of actin are detectable in worker ovarioles. Treatment of fourth-instar worker larvae with juvenile hormone rescues ovarioles from apoptosis and maintains the actin-spectrin association. Juvenile-hormone-dependent actin-spectrin interaction is thus one of the earliest steps in the differentiation of a polymorphic ovary. Plasticity in ovariole numbers as a result of hormone-dependent fusome formation may be a more widespread phenomenon in insects, extending beyond caste polymorphism in highly eusocial Hymenoptera.

Actins↗
PubMed2006

Degradation of spectrin via calpains in the ventral horn after transient spinal cord ischemia in rabbits.

In the present study, we investigated chronological changes of mu-calpain, m-calpain and cleaved spectrin alphaII immunoreactivity in the ventral horn after transient spinal cord ischemia to investigate relationship between calpains and vulnerability to ischemia using abdominal aorta occlusion model in rabbits. Spinal cord sections at the level of L(7) were immunostained with calpains and cleaved spectrin alphaII monoclonal antibodies. mu-Calpain and m-calpain immunoreactivity was significantly increased in the ischemic ventral horn at 30 min and 1 h after ischemia/reperfusion, respectively. Thereafter, they were decreased with time after ischemia/reperfusion: at 48 h after ischemia, their immunoreactivities nearly disappeared in the ischemic ventral horn. Cleaved spectrin alphaII immunoreactivity was significantly increased in the ventral horn of spinal cord at 12 h after ischemia/reperfusion, and thereafter, its immunoreactivity was decreased with time after ischemia/reperfusion. In addition, spectrin alphaII protein level (280 kDa) was decreased from 12 h after ischemia/reperfusion; in contrast, cleaved spectrin alphaII protein level (150 kDa) was significantly increased at 12 h after ischemia/reperfusion. In conclusion, our observations in this study indicate that calpain is associated with neuronal degeneration in the ventral horn at early time after transient spinal cord ischemia via the proteolysis of spectrin alphaII.

Animals↗
PubMed1978

Erythrocyte actin and spectrin. Interactions with muscle contractile and regulatory proteins.

Actin and spectrin were isolated from washed red blood cell membranes. Spectrin bound and polymerized erythrocyte actin in the absence of potassium. Spectrin coated into polystyrene latex particles bound 8--9 mol of erythrocyte actin per mol of spectrin when actin was in its depolymerized state. Spectrin enhanced the interaction of erythrocyte actin with muscle myosin as manifested by changes in Mg2+-ATPase activity. A similar enhancement also was observed with muscle alpha-actinin while muscle tropomyosin abolished these effects. The data suggest that spectrin may play the role of polymerizing factor as well as the anchoring site for erythrocyte actin just as alpha-actinin is the anchoring site for actin filaments in muscle and other non-muscle cells.

Actinin↗
PubMed1983

Binding of autologous IgG to human red blood cells before and after ATP-depletion. Selective exposure of binding sites (autoantigens) on spectrin-free vesicles.

Binding of autologous IgG to fresh, ATP-depleted red blood cells as well as to spectrin-free vesicles was studied by a non-equilibrium binding assay using 125I-iodinated protein A from Staphylococcus aureus. IgG binding was 14-times higher to spectrin-free vesicles than to ATP-maintaining red blood cells and 4-times higher than to ATP-depleted erythrocytes from which these vesicles were released. Protein A binding to vesicles that were released from washed and nutrient-deprived erythrocytes, was dependent on added autologous IgG. However, spectrin-free vesicles that were spontaneously released from erythrocytes conserved in whole blood, bound similar amounts of protein A with or without added autologous IgG (0.45-0.55 ng/micrograms band 3 protein). These findings demonstrate that opsonization of spectrin-free vesicles by autologous IgG occurs not only in the test tube, but also under blood blank conditions. The binding characteristics of IgG to spectrin-free vesicles are indicative of a natural autoantibody rather than an unspecific binding of autologous IgG. The preferential binding of IgG to spectrin-free vesicles implies a selective exposure of corresponding autoantigens in membrane regions that have lost cytoskeletal anchorage and bud off.

Adenosine Triphosphate↗
PubMed1981

Purification of a trypsin-insensitive fragment of spectrin from human erythrocyte membranes.

When spectrin is treated with trypsin, a series of polypeptide fragments is generated, One particular fragment having an approximate molecular weight of 80 000 constitutes 18% of the trypsin-digested mixture and is trypsin-insensitive. This fragment has been isolated and purified by gel filtration followed by ion-exchange chromatography. The molecular weight of the fragment, as seen from sedimentation equilibrium measurements and from gel electrophoresis, both in the presence and absence of detergent, is close to 80 000. There was no evidence of self-association under the conditions used. Changes in the specific rotation at 365 nm were used to detect temperature-dependent conformation changes in the fragment and to compare these changes with those in the intact spectrin molecule. The fragment undergoes temperature-dependent transitions centered at 46 and 58 degrees C, similar to those in intact spectrin (49 and 55 degrees C). Although the thermal transitions exhibited by intact spectrin are markedly salt-dependent, those shown by the fragment are not. ORD (optical rotary dispersion) measurements indicate 53% apparent alpha-helix in the fragment, compared to 68% in intact spectrin. Antibodies raised against the fragment cross-react only with band 1, the largest polypeptide of spectrin, indicating that the fragment is derived from band 1.

Electrophoresis, Polyacrylamide Gel↗
PubMed1984

The interaction of calmodulin with human and avian spectrin.

An air-driven ultracentrifuge was used to investigate the calcium-dependent interaction of 125I-calmodulin with human and avian spectrins. The equilibrium constants (Ka) for the interaction between calmodulin and human spectrin dimer and tetramer under non-denaturing conditions were estimated to be 4.6 X 10(4) M-1 and 7.3 X 10(4) M-1, respectively. The denaturation of human spectrin by urea (5 M) increased the Ka for calmodulin to 4.6 X 10(5) M-1. The value of Ka for the interaction of calmodulin with avian spectrin dimer under non-denaturing conditions was 5.1 X 10(5) M-1. A bifunctional reagent cross-linked both avian spectrin and human spectrin to calmodulin in a calcium-dependent manner.

Adenosine Triphosphatases↗
PubMed1992

Developmental expression of brain beta-spectrin isoform messenger RNAs.

We have investigated the expression of brain beta SpIIa and beta SpIb (previously referred to as the beta-subunits of brain spectrin (240/235) and brain spectrin (240/235E), respectively) during mouse brain development. The 9 kb transcript which encodes beta SpIIa is present in fetal mouse brain tissue and increases to a maximal level in a 30-day-old mouse. There is a coordinate accumulation of the 7.8 kb alpha SpIIa mRNA (with beta SpIIa) during mouse brain development. The coordinate expression of alpha SpIIa and beta SpIIa at the mRNA and protein level allows formation of (alpha SpIIa/beta SpIIa)2 tetramers (brain spectrin(240/235)) early in premitotic neuronal development; and avoids turnover of unassembled alpha and beta-subunits. An 11 kb transcript which encodes beta SpIb is not produced in embryonic tissue, and is first seen in a 6-day-old mouse. The protein translation products beta SpIIa and beta SpIb have previously been demonstrated by our laboratory to first appear in fetal mouse brain tissue and at postnatal day 6-8, respectively [J. Neurosci., 7 (1987) 864-874]. The expression of beta SpIb mRNA on postnatal day 6-8, and the appearance of brain spectrin(240/235E) in postmitotic and postmigratory neurons of the cerebellum at this same time; suggests that brain spectrin(240/235E) is involved in differentiated functions of the neuron (formation of cell-cell contacts, formation of dendritic processes and postsynaptic contacts). Thus, the data from the present study demonstrates that the expression of these two neuronal beta-spectrin isoforms is regulated at the level of mRNA expression.

Animals↗
PubMed1981

Spectrin extractability from erythrocyte in Duchenne muscular dystrophies and the effect of proteases on erythrocyte ghosts.

We studied the erythrocyte membrane proteins from patients with Duchenne muscular dystrophy (DMD) using SDS-polyacrylamide gel electrophoresis. Our observations were the following: (1) The electrophoretic densitogram of freshly prepared DMD-ghosts was similar to that of controls. After the extraction of spectrin from ghosts with 1 mmol/l EDTA, pH 8.0, the unextractable spectrin remained more firmly bound in the DMD ghost residues than in controls. Extractability of spectrin from DMD ghosts was decreased about 20%. In addition, several minor bands were detected between spectrin and Band 3 in the DMD ghost residues (treated ghosts). (2) Ca2+-activated, neutral protease reacted more effectively with spectrin of DMD ghosts and ATP-depleted ghosts than with that of controls. (3) Erythrocyte actin (Band 5) of DMD ghosts was more fragile than that of controls and of ATP-depleted actin in the EDTA extracts. Gradually, partial degradation of actin was observed for three weeks at 4 degrees C. (4) The intracellular ATP level and the activities of membrane-bound (Mg2+--Ca2+) ATPases in DMD erythrocytes were unchanged. We suggest that spectrin from DMD ghosts as well as actin may be subject to increased degradation.

Actins↗
PubMed1985

Spectrin extractability from erythrocytes in Duchenne muscular dystrophy patients and carriers and in other myopathies.

Spectrin extractability was measured in the erythrocyte membranes from patients with Duchenne Muscular Dystrophy (DMD), from DMD definite carriers (in whom serum creatine kinase (CK) was also measured) and patients affected by other myopathies. After the extraction of spectrin from ghosts with EDTA, membrane proteins were examined using sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Spectrin extractability was also investigated in the presence of an excess of calcium. Spectrin extraction from erythrocyte ghosts was significantly reduced with respect to controls in DMD patients, in DMD definite carriers and in patients affected by limb-girdle dystrophy, but not in patients suffering from other non-dystrophic myopathies. Fifty percent of DMD definite carriers showed a reduced extraction of spectrin and some of them had normal serum CK. Reduced extractability was also observed in red blood cells incubated in media containing excess calcium. Our results could suggest that reduced spectrin extractability is connected with a modification of intracellular calcium levels.

Adolescent↗
PubMed1989

A spectrin-like protein present on membranes of Amoeba proteus as studied with monoclonal antibodies.

Monoclonal antibodies against a spectrin-like membrane-associated protein of xD amoebae. (Amoeba proteus) were used to determine the distribution of the protein and some of its characteristics. A total of 34 monoclonal antibodies recognizing different epitopes of the protein were obtained, of which seven stained cell membranes by indirect immunofluorescence. The spectrin-like protein had two subtypes of 225 and 220 kDa and several monoclonal antibodies cross-reacted with human erythrocyte spectrin when checked by indirect immunofluorescence staining and immunoblotting. Some of the antibodies also cross-reacted with antigens in HeLa cells and chick embryo fibroblasts. Polyclonal and monoclonal antibodies against Drosophila and human erythrocyte spectrins cross-reacted with the spectrin-like protein from amoebae. On the basis of these results, it was concluded that the protein is a spectrin. The protein was found on most cellular membranes of amoebae, including the plasma, nuclear, and phagosomal membranes, as well as symbiosome membranes.

Amoeba↗
PubMed1992

Changes in polyamine levels and spectrin degradation following kainate-induced seizure activity: effect of difluoromethylornithine.

The induction of ornithine decarboxylase (ODC) in adult CNS and the resulting changes in polyamine levels are often observed under conditions associated with activation of NMDA receptors, calpain stimulation and spectrin degradation. The present study was directed at evaluating the links between these two sets of events. We measured the effects of an acute treatment of adult rats with difluoromethylornithine (DFMO), an irreversible inhibitor of ODC, on biochemical alterations following kainate-induced seizure activity. Beside ODC activity and polyamine levels, we assayed the in situ spectrin degradation and the in vitro binding of 3H-Ro5-4864, a ligand for the peripheral benzodiazepine binding sites which is a good marker of glial proliferation, at various time intervals following systemic kainic acid (KA) injection. Kainate-induced seizure activity was followed by a transient increase in ODC activity, a long-lasting increase in putrescine levels and spectrin degradation, and a delayed increase in 3H-Ro5-4864 binding, mainly in hippocampus and piriform cortex. Treatment of the animals with DFMO markedly reduced the increase in putrescine levels up to 7 days after KA injection. It also reduced the increase in spectrin breakdown observed at 16 h but not at 4 and 7 days after KA injection. Finally, it did not modify the increase in 3H-Ro5-4864 binding measured 4 and 7 days after KA injection. The levels of putrescine were positively correlated with the extent of spectrin proteolysis in KA-treated animals whether or not they were treated with DFMO, at 16 h but not at 7 days after KA injection. The results indicate that the extent of spectrin breakdown observed shortly after KA-induced seizure activity is causally related to the changes in ODC activity and putrescine levels. Although the data are consistent with the idea that putrescine could be a marker for acute pathology, they do not support a role for polyamines in delayed neurotoxicity.

Animals↗
PubMed1986

Selective detection of rapid motions in spectrin by NMR.

Human erythrocyte spectrin molecules exhibit relatively sharp (30-50 Hz) proton NMR signals in the aliphatic region. A standard solvent presaturation pulse sequence that also partially suppresses the broad envelope from protons with rigid structures in spectrin and selectively enhances the sharp resonances has been used to characterize the behavior of these resonances. The overall resonance pattern strongly resembles that of the denatured spectrin. The observed spectra are also quite similar to the line-broadened spectrum from a mixture of amino acids that corresponds to the composition of the spectrin molecule. These data indicate the existence of regions exhibiting rapid internal motions within the intact spectrin molecule, and suggest that the amino acid composition of the residues giving rise to the sharp resonances is quite similar to that of the full spectrin molecule.

Actins↗
PubMed1988

Activation induces a rapid reorganization of spectrin in lymphocytes.

Lymphocyte activation results in a rapid reorganization of the cytoskeletal protein spectrin. Immediately following an activation signal, there is fragmentation of a spectrin-rich cytoplasmic structure and subsequent translocation of the fragments to defined areas of the plasma membrane in both antigen-specific T cell hybridomas and lymph node T cells. These dramatic changes have been documented by light and electron microscopic immunolocalization and by immunoblot analysis of plasma membrane-enriched preparations. A T cell hybridoma variant lacking the spectrin-rich cytoplasmic structure of the parental line does not redistribute spectrin and produces little or no IL-2 in response to antigen-dependent activation. This suggests a functional link between spectrin distribution and activation potential. We propose that the cytoplasmic structure functions as an organizing center or reservoir for spectrin that is sensitive to signaling at the cell surface.

Animals↗