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PubMed1997

Intragenic duplication and divergence in the spectrin superfamily of proteins.

Many structural, signaling, and adhesion molecules contain tandemly repeated amino acid motifs. The alpha-actinin/spectrin/dystrophin superfamily of F-actin-crosslinking proteins contains an array of triple alpha-helical motifs (spectrin repeats). We present here the complete sequence of the novel beta-spectrin isoform beta(Heavy)-spectrin (beta H). The sequence of beta H supports the origin of alpha- and beta-spectrins from a common ancestor, and we present a novel model for the origin of the spectrins from a homodimeric actin-crosslinking precursor. The pattern of similarity between the spectrin repeat units indicates that they have evolved by a series of nested, nonuniform duplications. Furthermore, the spectrins and dystrophins clearly have common ancestry, yet the repeat unit is of a different length in each family. Together, these observations suggest a dynamic period of increase in repeat number accompanied by homogenization within each array by concerted evolution. However, today, there is greater similarity of homologous repeats between species than there is across repeats within species, suggesting that concerted evolution ceased some time before the arthropod/vertebrate split. We propose a two-phase model for the evolution of the spectrin repeat arrays in which an initial phase of concerted evolution is subsequently retarded as each new protein becomes constrained to a specific length and the repeats diverge at the DNA level. This evolutionary model has general applicability to the origins of the many other proteins that have tandemly repeated motifs.

Actinin↗
PubMed1980

Membrane orientation of sheep spectrin.

Based primarily on studies of human erythrocytes, current theories of the structure and organization of erythrocyte membrane localize spectrin to the membrane cytoplasmic surface. Affinity purified anti-sheep spectrin antibodies were used in indirect immunofluorescence studies of intact erythrocytes from various vertebrate species and inside-out and right-side-out impermeable sheep erythrocyte vesicles. This investigation detected immunologically reactive external and potentially transmembranal determinant(s) of the sheep erythrocyte spectrin "assembly." Parallel studies using anti-sheep and anti-human spectrin antibodies, as well as 125I surface-labelling studies of intact sheep and human erythrocytes, indicated that this particular membrane orientation of spectrin was evident in sheep but not in human erythrocytes. Antisera containing antibodies to the external portion of this spectrin "assembly" demonstrated external fluorescence to a variable degree on some, but not all, vertebrate erythrocytes surveyed, confirming that the sheep erythrocyte was not the only exception. It is suggested that there may be subtle species variability in the intermolecular associations of the spectrin "assembly" with(in) the erythrocyte membrane not requiring alterations of the spectrin molecule itself.

Animals↗
PubMed1984

A spectrin-like protein from mouse brain membranes: phosphorylation of the 235,000-dalton subunit.

A mouse brain spectrin-like protein, which was an immunoreactive analogue of erythrocyte spectrin, has been isolated from demyelinated membranes. This spectrin analogue was a 10.5 S, 972,000 molecular weight (Mr) (alpha beta)2 tetramer containing subunits of 240,000 (alpha) and 235,000 (beta) Mr. We demonstrated that in vivo only the 235,000 Mr beta subunit of the mouse brain spectrin-like protein was phosphorylated, which was an analogous situation to mouse erythrocyte spectrin in which only the 220,000 Mr beta subunit was phosphorylated. Incubation of isolated membrane fractions with [gamma-32P]ATP +/- adenosine 3',5'-cyclic monophosphate (cAMP) indicated that mouse brain spectrin-like protein, mouse erythrocyte spectrin, and human erythrocyte spectrin's beta subunits were all phosphorylated in vitro by membrane-associated cAMP-independent protein kinases.

Animals↗
PubMed2001

Defective spectrin integrity and neonatal thrombosis in the first mouse model for severe hereditary elliptocytosis.

Mutations affecting the conversion of spectrin dimers to tetramers result in hereditary elliptocytosis (HE), whereas a deficiency of human erythroid alpha- or beta-spectrin results in hereditary spherocytosis (HS). All spontaneous mutant mice with cytoskeletal deficiencies of spectrin reported to date have HS. Here, the first spontaneous mouse mutant, sph(Dem)/ sph(Dem), with severe HE is described. The sph(Dem) mutation is the insertion of an intracisternal A particle element in intron 10 of the erythroid alpha-spectrin gene. This causes exon skipping, the in-frame deletion of 46 amino acids from repeat 5 of alpha-spectrin and alters spectrin dimer/tetramer stability and osmotic fragility. The disease is more severe in sph(Dem)/sph(Dem) neonates than in alpha-spectrin-deficient mice with HS. Thrombosis and infarction are not, as in the HS mice, limited to adults but occur soon after birth. Genetic background differences that exist between HE and HS mice are suspect, along with red blood cell morphology differences, as modifiers of thrombosis timing. sph(Dem)/sph(Dem) mice provide a unique model for analyzing spectrin dimer- to-tetramer conversion and identifying factors that influence thrombosis.

Age Factors↗
PubMed1994

Beta heavy-spectrin has a restricted tissue and subcellular distribution during Drosophila embryogenesis.

The components of the membrane skeleton play an important role in maintaining membrane structure during the dynamic changes in cell shape that characterize development. beta Heavy-spectrin is a unique beta-spectrin from Drosophila melanogaster that is closer in size (M(r) = 430 x 10(3)) to dystrophin than to other beta-spectrin members of the spectrin/alpha-actinin/dystrophin gene super-family. Here we establish that both the subcellular localization of the beta Heavy-spectrin protein and the tissue distribution of beta Heavy-spectrin transcript accumulation change dramatically during embryonic development. Maternally loaded protein is uniformly distributed around the plasma membrane of the egg. During cellularization it is associated with the invaginating furrow canals and in a region of the lateral membranes at the apices of the forming cells (apicolateral). During gastrulation the apicolateral staining remains and is joined by a new apical cap, or plate, of beta Heavy-spectrin in areas where morphogenetic movements occur. These locations include the ventral and cephalic furrows and the posterior midgut invagination. Thus, dynamic rearrangement of the subcellular distribution of the protein is precisely coordinated with changes in cell shape. Zygotic message and protein accumulate after the germ band is fully extended, in the musculature, epidermis, hindgut, and trachea of the developing embryo. beta Heavy-spectrin in the epidermis, hindgut, and trachea is apically localized, while the protein in the somatic and visceral musculature is not obviously polarized. The distribution of beta Heavy-spectrin suggests roles in establishing an apicolateral membrane domain that is known to be rich in intercellular junctions and in establishing a unique membrane domain associated with contractile processes.

Animals↗
PubMed1997

alpha-Spectrin is required for ovarian follicle monolayer integrity in Drosophila melanogaster.

To understand the role of the spectrin-based membrane skeleton in generating epithelial polarity, we characterized the distribution of membrane skeletal components in Drosophila ovarian follicle cells and in somatic clones of mutant cells that lack alpha-spectrin. Immunolocalization data reveal that wild-type follicle cells contain two populations of spectrin heterodimers: a network of alphabeta heterodimers concentrated on the lateral plasma membrane and an alphabetaH population targeted to the apical surface. Induction of somatic clones lacking alpha-spectrin leads to follicle cell hyperplasia. Surprisingly, elimination of alpha-spectrin from follicle cells does not appear to prevent the assembly of conventional beta-spectrin and ankyrin at the lateral domain of the follicle cell plasma membrane. However, the alpha-subunit is essential for the correct localization of betaH-spectrin to the apical surface. As a consequence of disrupting the apical membrane skeleton a distinct sub population of follicle cells undergoes unregulated proliferation which leads to the loss of monolayer organization and disruption of the anterior-posterior axis of the oocyte. These results suggest that the spectrin-based membrane skeleton is required in a developmental pathway that controls follicle cell monolayer integrity and proliferation.

Animals↗
PubMed2006

Stimulation of Galphaq-coupled M1 muscarinic receptor causes reversible spectrin redistribution mediated by PLC, PKC and ROCK.

Spectrin is a cytoskeletal protein that plays a role in formation of the specialized plasma membrane domains. However, little is known of the molecular mechanism that regulates responses of spectrin to extracellular stimuli, such as activation of G-protein-coupled receptor (GPCR). We have found that alphaII spectrin is a component of the Galpha(q/11)-associated protein complex in CHO cells stably expressing the M1 muscarinic receptor, and investigated the effect of activation of GPCR on the cellular localization of yellow-fluorescent-protein-tagged alphaII spectrin. Stimulation of Galpha(q/11)-coupled M1 muscarinic receptor triggered reversible redistribution of alphaII spectrin following a rise in intracellular Ca2+ concentration. This redistribution, accompanied by non-apoptotic membrane blebbing, required an intact actin cytoskeleton and was dependent on activation of phospholipase C, protein kinase C, and Rho-associated kinase ROCK. Muscarinic-agonist-induced spectrin remodeling appeared particularly active at localized domains, which is clear contrast to that caused by constitutive activation of ROCK and to global rearrangement of the spectrin lattice caused by changes in osmotic pressure. These results suggest a role for spectrin in providing a dynamic and reversible signaling platform to the specific domains of the plasma membrane in response to stimulation of GPCR.

Animals↗
PubMed2000

Spectrin tethers and mesh in the biosynthetic pathway.

The paradox of how the Golgi and other organelles can sort a continuous flux of protein and lipid but maintain temporal and morphological stability remains unresolved. Recent discoveries highlight a role for the cytoskeleton in guiding the structure and dynamics of organelles. Perhaps one of the more striking, albeit less expected, of these discoveries is the recognition that a spectrin skeleton associates with many organelles and contributes to the maintenance of Golgi structure and the efficiency of protein trafficking in the early secretory pathway. Spectrin interacts directly with phosphoinositides and with membrane proteins. The small GTPase ARF, a key player in Golgi dynamics, regulates the assembly of the Golgi spectrin skeleton through its ability to control phosphoinositide levels in Golgi membranes, whereas adapter molecules such as ankyrin link spectrin to other membrane proteins. Direct interactions of spectrin with actin and centractin (ARP1) provide a link to dynein, myosin and presumably other motors involved with intracellular transport. Building on the recognized ability of spectrin to organize macromolecular complexes of membrane and cytosolic proteins into a multifaceted scaffold linked to filamentous structural elements (termed linked mosaics), recent evidence supports a similar role for spectrin in organelle function and the secretory pathway. Two working models accommodate much of the available data: the Golgi mesh hypothesis and the spectrin ankyrin adapter protein tethering system (SAATS) hypothesis.

Animals↗
PubMed2000

The muscle regulatory and structural protein MLP is a cytoskeletal binding partner of betaI-spectrin.

Muscle LIM protein (MLP) is a striated muscle-specific factor that enhances myogenic differentiation and is critical to maintaining the structural integrity of the contractile apparatus. The ability of MLP to regulate myogenesis is particularly interesting since it exhibits multiple subcellular localizations, being found in both nuclear and cytoplasmic compartments. Despite extensive biochemical analyses on MLP, the mechanism(s) by which it influences the myogenic program remains largely undefined. To further examine the role of MLP as a positive myogenic regulator, a yeast two-hybrid screen was employed to identify cytoplasmic-associated MLP binding partners. From this screen, the cytoskeletal protein betaI-spectrin was isolated. Protein interaction assays demonstrate that MLP and betaI-spectrin associate with one another in vivo as well as when tested under several in vitro binding conditions. betaI-spectrin binds specifically to MLP but not to the MLP related proteins CRP1 and CRP2 or to other LIM domain containing proteins. The MLP:beta-spectrin interaction is mediated by the second LIM motif of MLP and by repeat 7 of beta-spectrin. Confocal microscopy studies also reveal that MLP co-localizes with beta-spectrin at the sarcolemma overlying the Z- and M-lines of myofibrils in both cardiac and skeletal muscle tissue. Given that beta-spectrin is a known costamere protein, we propose that sarcolemma-associated MLP also serves as a key costamere protein, stabilizing the association of the contractile apparatus with the sarcolemma by linking the beta-spectrin network to the alpha-actinin crosslinked actin filaments of the myofibril.

Animals↗
PubMed2001

Na,K-ATPase in skeletal muscle: two populations of beta-spectrin control localization in the sarcolemma but not partitioning between the sarcolemma and the transverse tubules.

We used immunological approaches to study the factors controlling the distribution of the Na,K-ATPase in fast twitch skeletal muscle of the rat. Both alpha subunits of the Na,K-ATPase colocalize with beta-spectrin and ankyrin 3 in costameres, structures at the sarcolemma that lie over Z and M-lines and in longitudinal strands. In immunoprecipitates, the alpha1 and alpha2 subunits of the Na,K-ATPase as well as ankyrin 3 associate with beta-spectrin/alpha- fodrin heteromers and with a pool of beta-spectrin at the sarcolemma that does not contain alpha-fodrin. Myofibers of mutant mice lacking beta-spectrin (ja/ja) have a more uniform distribution of both the alpha1 and alpha2 subunits of the Na,K-ATPase in the sarcolemma, supporting the idea that the rectilinear sarcomeric pattern assumed by the Na,K-ATPase in wild-type muscle requires beta-spectrin. The Na,K-ATPase and beta-spectrin are distributed normally in muscle fibers of the nb/nb mouse, which lacks ankyrin 1, suggesting that this isoform of ankyrin is not necessary to link the Na,K-ATPase to the spectrin-based membrane skeleton. In immunofluorescence and subcellular fractionation experiments, the alpha2 but not the alpha1 subunit of the Na,K-ATPase is present in transverse (t-) tubules. The alpha1 subunit of the pump is not detected in increased amounts in the t-tubules of muscle from the ja/ja mouse, however. Our results suggest that the spectrin-based membrane skeleton, including ankyrin 3, concentrates both isoforms of the Na,K-ATPase in costameres, but that it does not play a significant role in restricting the entry of the alpha1 subunit into the t-tubules.

Animals↗
PubMed2001

Drosophila alpha- and beta-spectrin mutations disrupt presynaptic neurotransmitter release.

Spectrins are plasma membrane-associated cytoskeletal proteins implicated in several aspects of synaptic development and function, including presynaptic vesicle tethering and postsynaptic receptor aggregation. To test these hypotheses, we characterized Drosophila mutants lacking either alpha- or beta-spectrin. The Drosophila genome contains only one alpha-spectrin and one conventional beta-spectrin gene, making it an ideal system to genetically manipulate spectrin levels and examine the resulting synaptic alterations. Both spectrin proteins are strongly expressed in the Drosophila neuromusculature and highly enriched at the glutamatergic neuromuscular junction. Protein null alpha- and beta-spectrin mutants are embryonic lethal and display severely disrupted neurotransmission without altered morphological synaptogenesis. Contrary to current models, the absence of spectrins does not alter postsynaptic glutamate receptor field function or the ultrastructural localization of presynaptic vesicles. However, the subcellular localization of numerous synaptic proteins is disrupted, suggesting that the defects in presynaptic neurotransmitter release may be attributable to inappropriate assembly, transport, or localization of proteins required for synaptic function.

Animals↗
PubMed1991

[The production of monoclonal anti-human spectrin antibody cross-reactive with single-stranded DNA].

Five monoclonal anti-human red blood cell (RBC) antibodies (all IgM kappa type) were produced by immunizing BALB/c mouse with human O-type RBC. Solid phase enzyme linked immunosorbent assays (ELISAs) were used for studying the reactivities of monoclonal antibodies against RBC, DNA, cardiolipin, dermatan sulfate and spectrin. Because two monoclonal antibodies (1B1A2E5, 1B1B2G7) of these antibodies also reacted with heat-denatured DNA (ssDNA) derived from calf thymus, salmon sperm and human white blood cell, the cross-reactivities of two monoclonal antibodies were analyzed. They reacted with spectrin, one of the RBC cytoskeleton proteins, by western blotting using RBC ghost protein and ELISA using spectrin, but not react with other anionic antigens such as cardiolipin and dermatan sulfate. The anti-RBC activities of the two monoclonal antibodies were not changed by DNase I treatment, but were decreased by pronase E treatment of RBC ghost protein. And, the anti-ssDNA activities of these antibodies were abolished by DNase I treatment, but were not changed by pronase E treatment of DNA. The reactivities of these antibodies to RBC and ssDNA were inhibited by ssDNA, The reactivities of these antibodies to RBC and ssDNA were inhibited by ssDNA, RBC ghost protein and rabbit anti-mouse IgM antiserum, but were not inhibited by dsDNA, RBC, rabbit anti-mouse IgG antiserum, bovine serum albumin and spectrin in liquid phase. In inhibition test, spectrin in liquid phase did not inhibit the reaction for RBC or ssDNA of these antibodies. Complements were fixed to these antibodies in RBC, ssDNA and spectrin ELISA. In the view of the above results, it was concluded that the RBC antigen of the 2 monoclonal antibodies was directed against spectrin in solid phase, and that these antibodies were cross-reactive with both RBC (spectrin) and ssDNA (derived from calf thymus, salmon sperm and human white blood cell).

Animals↗
PubMed1991

Structure, calmodulin-binding, and calcium-binding properties of recombinant alpha spectrin polypeptides.

We examined the structure and the distribution of binding activities within bacterially produced fragments of Drosophila alpha spectrin. By electron microscopy, purified spectrin fragments resembled the corresponding regions of native spectrin. The contour lengths of recombinant spectrin molecules were proportional to the length of their coding sequences, which is consistent with current models of spectrin structure in which individual segments of the polypeptide contribute independently to the structure of the native molecule. We localized two sites at which calcium may regulate spectrin function. First, a site responsible for calmodulin binding to Drosophila alpha spectrin was identified near the junction of repetitive segments 14 and 15. Second, a domain of Drosophila alpha spectrin that includes two EF hand calcium-binding sequences bound 45Ca in blot overlay assays. EF hand sequences from a homologous domain of Drosophila alpha actinin did not bind calcium under the same conditions.

Actins↗
PubMed1985

Phosphorylation of ankyrin decreases its affinity for spectrin tetramer.

The effects of phosphorylation on the interaction between spectrin and ankyrin were investigated. Spectrin and ankyrin were phosphorylated using purified human erythrocyte membrane and cytosolic (casein kinase A) kinases. These two kinases have similar properties as well as activities toward spectrin and ankyrin. Both kinases catalyzed the incorporation of about 2 mol of phosphate/mol of spectrin and about 7 mol of phosphate/mol of ankyrin. These phosphates were incorporated primarily into seryl and threonyl residues of the proteins. The phosphopeptide maps of ankyrin phosphorylated by the membrane kinase and casein kinase A were identical. Binding studies indicate that ankyrin exhibits different affinities for spectrin dimers (KD = 2.5 +/- 0.9 X 10(-6) M) and tetramers (KD = 2.7 +/- 0.8 X 10(-7) M). These dissociation constants were not appreciably affected by the phosphorylation of spectrin. On the other hand, phosphorylation of ankyrin was found to significantly reduce its affinity for either phosphorylated or unphosphorylated spectrin tetramers (KD = 1.2 +/- 0.1 X 10(-6) M) but not spectrin dimers (KD = 2.5 +/- 0.4 X 10(-6) M). The same results were obtained using either the membrane kinase or casein kinase A as the phosphorylating enzyme. The above observation suggests that ankyrin phosphorylation may provide an important mechanism for the regulation of the erythrocyte membrane cytoskeletal network.

Ankyrins↗
PubMed1988

Proteolytic processing of human brain alpha spectrin (fodrin): identification of a hypersensitive site.

The processing of brain spectrin (fodrin) by calcium-dependent proteases at the postsynaptic membrane has been postulated to be one of the central molecular mechanisms underlying long-term potentiation (LTP). The effect of such processing on the structure and function of brain spectrin, and on spectrin's ability to organize or otherwise regulate receptor function remains unclear. To address these issues, human and bovine brain spectrin were digested under mild conditions with several proteases, and the resulting cleavage fragments analyzed by 2-dimensional chymotryptic 125I peptide mapping. These studies identify an underlying protease-resistant domain structure reminiscent of, yet distinctly different from, human erythroid spectrin. More importantly, fodrin is unusual for the presence of a single, proteolytically hypersensitive site in the center of the alpha subunit, which is the favored site of action by many proteases, including the calcium-dependent neutral proteases. This proteolytically hypersensitive site is a unique feature of alpha nonerythroid spectrin since it is absent from human erythrocyte spectrin and appears to be the site at which the molecule is processed in vivo. In addition, on the basis of gel overlay techniques, it appears that the hypersensitive site is also the site at which calmodulin binds to the alpha-subunit in a calcium-dependent manner. These studies thus establish at the molecular level 2 calcium-dependent mechanisms by which brain spectrin function might be regulated and provide a conceptual and methodological framework for further investigation into the function of this important molecule.

Brain↗
PubMed1985

The elasticity of spectrin-actin gels at high protein concentration.

Human erythrocyte spectrin of high purity was studied alone and mixed with rabbit skeletal actin by dynamic rheometry as a function of protein concentration at pH 7.4 and 24 degrees C. Pure spectrin had a very low storage modulus, G', increasing slightly with increase in protein concentration (approximately 3 dynes/cm at 25 mg/ml). In contrast, unpurified cytoskeletal extracts containing spectrin, actin, and band 4.1 showed a marked concentration dependence for G', increasing to 150 dynes/cm at 20 mg/ml. Mixtures of purified spectrin and skeletal actin at a weight ratio of 4:1 also showed G' markedly dependent on concentration (approximately 150-200 dynes/cm at 20 mg/ml). Maximum elasticity of spectrin-actin gels occurred at a molar ratio of actin monomers to spectrin tetramers of 14:1. We conclude that the reconstituted in vitro spectrin-actin network consists of actin fibers cross-linked by spectrin tetramers at regular intervals. The gel is rapidly reformed after mechanical disruption or thermal collapse, indicating that the polymer fibers are in equilibrium with the constituent monomers.

Acetone↗
PubMed1984

Brain ankyrin. Purification of a 72,000 Mr spectrin-binding domain.

Polypeptides of Mr = 190,000-220,000 that cross-react with erythrocyte ankyrin were detected in immunoblots of membranes from pig lens, pig brain, and rat liver. The cross-reacting polypeptides from brain were cleaved by chymotrypsin to fragments of Mr = 95,000 and 72,000 which are the same size as fragments obtained with erythrocyte ankyrin. The brain 72,000 Mr fragment associated with erythrocyte spectrin, and the binding occurred at the same site as that of erythrocyte ankyrin 72,000 Mr fragment since (a) brain 72,000 Mr fragment was adsorbed to erythrocyte spectrin-agarose and (b) 125I-labeled erythrocyte spectrin bound to brain 72,000 Mr fragment following transfer of the fragment from a sodium dodecyl sulfate gel to nitrocellulose paper, and this binding was displaced by erythrocyte ankyrin 72,000 Mr fragment. Brain 72,000 Mr fragment was purified about 400-fold by selective extraction and by continuous chromatography on columns attached in series containing DEAE-cellulose followed by erythrocyte spectrin coupled to agarose, and finally hydroxylapatite. The brain 72,000 Mr fragment was not derived from contaminating erythrocytes since peptide maps of pig brain and pig erythrocyte 72,000 Mr fragments were distinct. The amount of brain 72,000 Mr fragment was estimated as 0.28% of membrane protein or 39 pmol/mg based on radioimmunoassay with 125I-labeled brain fragment and antibody against erythrocyte ankyrin. Brain spectrin tetramer was present in about the same number of copies (30 pmol/mg of membrane protein) based on densitometry of Coomassie blue-stained sodium dodecyl sulfate gels. The binding site on brain spectrin for both brain and erythrocyte ankyrin 72,000 Mr fragments was localized by electron microscopy to the midregion of spectrin tetramers about 90 nM from the near end and 110 nM from the far end. These studies demonstrate the presence in brain membranes of a protein closely related to erythrocyte ankyrin, and are consistent with a function of the brain ankyrin as a membrane attachment site for brain spectrin.

Animals↗
PubMed1984

Mechanisms of cytoskeletal regulation. Modulation of aortic endothelial cell spectrin by the extracellular matrix.

Endothelial cells have a complex cytoskeleton that is responsive to a variety of stimuli such as shear and desquamative injury. The extracellular matrix is known to influence several aspects of cellular behavior, including attachment, spreading, and migration and may, in part, initiate and control vascular responses in growth, differentiation, wound repair, and neoplasia. It is likely that linkage between surface receptors responsible for sensing the matrix and the cytoskeleton may be relevant to understanding the mechanisms of these responses. Spectrin is a high-molecular-weight heterodimer recently identified in many cells that appears to link surface receptors to cortical actin filaments. We have confirmed the existence of spectrin in cultured aortic endothelial cells by metabolic labeling and immunoprecipitation and demonstrated that its organization and intracellular distribution is sensitive to the extracellular matrix. When bovine calf aortic endothelial cells (BAEC) are cultured to confluency on a fibronectin (Fn) substrate, they assume a flattened, spread morphology and exhibit a punctate spectrin distribution with no discernible peripheral localization. In contrast, BAECs cultured on a Type I/III collagen (I/III) substrate exhibit a fibrillar spectrin pattern with significant peripheral localization. When migrating cells were examined, the distribution of spectrin was strikingly different. The cells on the Fn substrate showed no changes in spectrin localization, whereas the cells on I/III exhibited a significant rearrangement, with spectrin being in a coarse fibrillar form, with the fibrils aligned parallel to the direction of migration. The differences in arrangement of this cytoskeletal component on the two substrata reflect the ability of the substrate to perturb the cytoskeletal organization and modulate some aspects of cell behavior such as spreading, proliferation, and migration. These data are consistent with the concept that the nonerythroid spectrins may function as transducers of information from membrane receptors to the cytoskeleton.

Animals↗