Contributions of the β‐subunit to spectrin structure and function

Coleman, Thomas R.; Fishkind, Douglas J.; Mooseker, Mark S.; Morrow, Jon S.

doi:10.1002/cm.970120406

Cited by 47 publications

(24 citation statements)

References 58 publications

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“…Thus the three-step in vitro cascade depicted here may have implications for our understanding of the control of receptor organization and plasma membrane dynamics in vivo. It has been hypothesized that the fodrin-based cortical cytoskeleton might serve as an organizer of topographic membrane domains, a targeting mechanism for vesicles containing membrane proteins, a stabilizer of the plasma membrane, and as a barrier to unregulated vesicle traffic (1). These processes probably involve transient changes in the plasticity of the cortical cytoskeleton and its linkage to membrane receptors and microfilaments (28).…”

Section: Methodsmentioning

confidence: 99%

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Calmodulin and calcium-dependent protease I coordinately regulate the interaction of fodrin with actin.

Harris

Morrow

1990

Proc. Natl. Acad. Sci. U.S.A.

116

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The calcium-dependent proteolysis of fodrin has been implicated in the regulation of secretion, neutrophil and platelet activation, and long-term potentiation in neurons. In vitro studies indicate that calcium-dependent protease I (calpain 1) cleaves fodrin in the middle of the a subunit and in the COOH-terminal third of the (I subunit. Cleavage at the 3 site requires calmodulin, which binds with high affinity to a single site in the a subunit. In vitro binding assays, nondenaturing gel electrophoresis, and velocity sedimentation identify a linkage between calcium-dependent protease I proteolysis of fodrin and the ability of calmodulin to regulate the selfassociation of fodrin and its interaction with actin. Three functional states appear to exist: (i) intact fodrin, which constitutively forms tetramers and binds F-actin; (ii) a-cleaved fodrin, which loses its ability to self-associate and bind F-actin in the presence of calmodulin; and (Wi) a,P-cleaved fodrin, a form that is incompetent to establish tetramers or bind actin. Because actin binding and fodrin self-association occur at opposite ends of the molecule, whereas calmodulin binds at its center, these results indicate that long-range interactions exist within fodrin. They also offer an example of how two calciumdependent regulatory processes may act synergistically to reversibly regulate a linkage between the membrane and the cytoskeleton.

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Section: Methodsmentioning

confidence: 99%

“…Fodrin is a ubiquitous cytoskeletal protein involved with organizing receptor domains and possibly the control of vesicle traffic at the plasma membrane (1). Central to its action is its ability to link integral membrane proteins to cortical actin filaments.…”

mentioning

confidence: 99%

Calmodulin and calcium-dependent protease I coordinately regulate the interaction of fodrin with actin.

Harris

Morrow

1990

Proc. Natl. Acad. Sci. U.S.A.

116

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“…βHeavy-spectrin isoforms do not bind to ankyrin (Coleman et al, 1989;Lee et al, 1997;Thomas et al, 1997), indicating that other interactions must mediate its recruitment to the membrane. We have previously reported that mutations in the karst locus, which produce truncated βH isoforms lacking the C-terminus and tetramerization site, do not detectably accumulate at the plasma membrane in epithelial cells (Medina et al, 2002;Zarnescu, 2000) (Fig.…”

mentioning

confidence: 99%

The C-terminal domain ofDrosophilaβHeavy-spectrin exhibits autonomous membrane association and modulates membrane area

Williams

MacIver

Klipfell

et al. 2004

Journal of Cell Science

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Current models of cell polarity invoke asymmetric cues that reorganize the secretory apparatus to induce polarized protein delivery. An important step in this process is the stabilization of the protein composition in each polarized membrane domain. The spectrin-based membrane skeleton is thought to contribute to such stabilization by increasing the half-life of many proteins at the cell surface. Genetic evidence is consistent with a negative role for Drosophila βHeavy-spectrin in endocytosis, but the inhibitory mechanism has not been elucidated. Here, we investigated the membrane binding properties of the C-terminal nonrepetitive domain of βHeavy-spectrin through its in vivo expression in transgenic flies. We found that this region is a membrane-association domain that requires a pleckstrin homology domain for full activity, and we showed for the first time that robust membrane binding by such a C-terminal domain requires additional contributions outside the pleckstrin homology. In addition, we showed that expression of the βHeavy-spectrin C-terminal domain has a potent effect on epithelial morphogenesis. This effect is associated with its ability to induce an expansion in plasma membrane surface area. The membrane expansions adopt a very specific bi-membrane structure that sequesters both the C-terminal domain and the endocytic protein dynamin. Our data provide supporting evidence for the inhibition of endocytosis by βHeavy-spectrin, and suggest that the C-terminal domain mediates this effect through interaction with the endocytic machinery. Spectrin may be an active partner in the stabilization of polarized membrane domains.

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“…For example, although the known a subunits are very similar to each other in molecular mass (-280 kDa), the molecular mass of known 13-spectrins range from 246 kDa to 430 kDa (1,2). In addition, diversity in the /8 subunits is thought to account for most of the distinctive structural and functional attributes of different spectrin isoforms (3,4).…”

mentioning

confidence: 99%

The complete sequence of Drosophila beta-spectrin reveals supra-motifs comprising eight 106-residue segments.

Byers

Brandin

Lue

et al. 1992

Proc. Natl. Acad. Sci. U.S.A.

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The a and P chains of spectrin are homologous, yet they have acquired different structural features that work in synergy to give the multimer its overall properties. The primary amino acid sequence of each spectrin subunit is dominated by tandemly repeated 106-residue motifs. By comparing the complete Drosophila f-spectrin sequence with other spectrins we have discovered evidence that a higher-order, 848-amino acid supra-motif is tandemly repeated in both aand .3-spectrin. These data argue that a-and (3-spectrin, rather than evolving independently from sequences encoding the ancestral 106-residue motifs, must have arisen after the establishment of a large supra-motif composed of eight of the 106-residue motifs. Our data suggest the segment structure of a progenitor gene that gave rise to both a-and 13-spectrin as well as dystrophin. The structural differences that evolved after the split between the a-and /3-spectrin genes confer the independent functions that exist in their products today.Spectrin is an important component of the membrane skeleton in most, if not all, cell types. The a and /3 subunits of spectrin are large, elongated polypeptides that have common evolutionary origins but have since acquired many distinct structural and functional attributes. For example, although the known a subunits are very similar to each other in molecular mass (-280 kDa), the molecular mass of known 13-spectrins range from 246 kDa to 430 kDa (1, 2). In addition, diversity in the /8 subunits is thought to account for most of the distinctive structural and functional attributes of different spectrin isoforms (3, 4).As first described by Speicher and Marchesi (5), a structural feature common to the a-and ,B-spectrin subunits is the presence of tandemly repeated 106-residue motifs that are also referred to as repeating units or segments (6). The repeating segments typically display a limited sequence similarity with one another and are defined by the presence of a consensus profile of conserved residues that occur at characteristic positions in each segment. Dystrophin and a-actinin, other members of the spectrin superfamily (7, 8), also contain homologous repetitive motifs. It has been postulated that a-spectrin arose by the serial duplication of an ancestral sequence that encoded the 106-residue segments, followed by the duplication of a larger block of DNA encoding several of these 106-residue segments (9-11). Here we present data showing that, rather than a simple duplication in a-spectrin alone, the repetitive regions of both present-day a-and P-spectrin genes were derived from a tandemly repeated supra-motif that encoded eight of the 106-amino acid motifs.tWe also find that the primary sequences of Drosophila and human ,B-spectrin are quite similar and coextensive except at their carboxyl-terminal ends. MATERIALS AND METHODSNested deletions of two cDNA clones, B15 and B32, that contain the complete coding region of Drosophila f8-spectrin were generated by exonuclease digestion essentially as described (12). Nucle...

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Contributions of the β‐subunit to spectrin structure and function

Cited by 47 publications

References 58 publications

Calmodulin and calcium-dependent protease I coordinately regulate the interaction of fodrin with actin.

Calmodulin and calcium-dependent protease I coordinately regulate the interaction of fodrin with actin.

The C-terminal domain ofDrosophilaβHeavy-spectrin exhibits autonomous membrane association and modulates membrane area

The complete sequence of Drosophila beta-spectrin reveals supra-motifs comprising eight 106-residue segments.

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