Properties of brain spectrin (fodrin)

Burns, Nigel R.; Ohanian, Vasken; Gratzer, Walter

doi:10.1016/0014-5793(83)80140-9

Cited by 57 publications

(27 citation statements)

References 22 publications

(16 reference statements)

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“…Although we can conclude that the present primary structure is consistent with the predictions of the Speicher-Marchesi model, it is difficult to predict just three helices within the repeats. Overall, the sequence data supports the conclusion from spectroscopic studies (Burns et al, 1983) of the high c~-helicity of spectrin.…”

Section: Secondary Structuresupporting

confidence: 84%

Primary structure of the brain alpha-spectrin [published erratum appears in J Cell Biol 1989 Mar;108(3):following 1175]

Wasenius

1989

The Journal of Cell Biology

157

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Abstract. We have determined the nucleotide sequence coding for the chicken brain a-spectrin. It is derived both from the cDNA and genomic sequences, comprises the entire coding frame, 5' and 3' untranslated sequences, and terminates in the poly(A)-tail. The deduced amino acid sequence was used to map the domain structure of the protein. The a-chain of brain spectrin contains 22 segments of which 20 correspond to the repeat of the human erythrocyte spectrin (Speicher, D. W., and V. T. Marchesi. 1984. Nature (Lond.). 311:177-180.), typically made of 106 residues. These homologous segments probably account for the flexible, rod-like structure of spectrin. Secondary structure prediction suggests predominantly a-helical structure for the entire chain.Parts of the primary structure are excluded from the repetitive pattern and they reside in the middle part of the sequence and in its COOH terminus. Search for homology in other proteins showed the presence of the following distinct structures in these nonrepetitive regions: (a) the COOH-terminal part of the molecule that shows homology with a-actinin, (b) two typical EF-hand (i.e., Ca:*-binding) structures in this region, (c) a sequence close to the EF-hand that fulfills the criteria for a calmodulin-binding site, and (d) a domain in the middle of the sequence that is homologous to a NH2-terminal segment of several src-tyrosine kinases and to a domain of phospholipase C. These regions are good candidates to carry some established as well as some yet unestablished functions of spectrin. Comparative analysis showed that a-spectrin is well conserved across the species boundaries from Xenopus to man, and that the human erythrocyte a-spectrin is divergent from the other spectrins.

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Section: Secondary Structuresupporting

confidence: 84%

Primary structure of the brain alpha-spectrin [published erratum appears in J Cell Biol 1989 Mar;108(3):following 1175]

Wasenius

1989

The Journal of Cell Biology

157

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“…3 Ca 2ϩ extrusion carried out by PMCA in the 4.1R KO and WT myocytes was therefore investigated. Using experimental conditions where SR Ca 2ϩ uptake, Na ϩ / Ca 2ϩ exchanger (NCX) and mitochondrial uptake are inhibited 14 no significant difference between the groups could be detected (time constant of decline: 4.1R KO, 8.1Ϯ0.6 seconds [19]; WT: 9.8Ϯ0.8 seconds [14]; PϭNS), suggesting that PMCA is not involved in the changes in Ca 2ϩ transients observed in protein 4.1R KO myocytes.…”

Section: Resultsmentioning

confidence: 99%

“…Figure 8E through 8G show that the expression of the actin-binding proteins ␣-actinin, spectrin, and tropomyosin (TM) is also unaltered: of these, spectrin and TM also bind 4.1R. 19,20 We also tested whether alterations in ion transporter activity were associated with changes in protein expression. Figure 8H shows that the level of the ␣-subunit of NaV1.5 is reduced by approximately 40% in 4.1R KO myocardium.…”

mentioning

confidence: 99%

Cytoskeletal Protein 4.1R Affects Repolarization and Regulates Calcium Handling in the Heart

Stagg

Carter²,

Sohrabi

et al. 2008

Circulation Research

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Abstract-The 4.1 proteins are a family of multifunctional adaptor proteins. They promote the mechanical stability of plasma membranes by interaction with the cytoskeletal proteins spectrin and actin and are required for the cell surface expression of a number of transmembrane proteins. Protein 4.1R is expressed in heart and upregulated in deteriorating human heart failure, but its functional role in myocardium is unknown. To investigate the role of protein 4.1R on myocardial contractility and electrophysiology, we studied 4.1R-deficient (knockout) mice (4.1R KO). ECG analysis revealed reduced heart rate with prolonged Q-T interval in 4.1R KO. No changes in ejection fraction and fractional shortening, assessed by echocardiography, were found. The action potential duration in isolated ventricular myocytes was prolonged in 4.1R KO. Ca 2ϩ transients were larger and slower to decay in 4.1R KO. The sarcoplasmic reticulum Ca 2ϩ content and Ca 2ϩ sparks frequency were increased. The Na ϩ /Ca 2ϩ exchanger current density was reduced in 4.1R KO. The transient inward current inactivation was faster and the persistent Na ϩ current density was increased in the 4.1R KO group, with possible effects on action potential duration. Although no major morphological changes were noted, 4.1R KO hearts showed reduced expression of NaV1.5␣ and increased expression of protein 4.1G. Our data indicate an unexpected and novel role for the cytoskeletal protein 4.1R in modulating the functional properties of several cardiac ion transporters with consequences on cardiac electrophysiology and with possible significant roles during normal cardiac function and disease. Key Words: cardiac cytoskeleton Ⅲ ion transporter regulation Ⅲ EC coupling T he cardiac cytoskeleton is important in conferring stability to the myocardium, in sensing the mechanical stretch, and in coordinating the assembly of cellular structures and intercellular signaling. 1 One group of cytoskeletal proteins, the spectrin-and ankyrin-associated system, is involved in the complex interplay between actin, spectrin, and various ion transporters in relation to the regulation of intracellular [Ca 2ϩ ]. 2 Beta II spectrin, muscle LIM-only protein, and ankyrin B and G have all been associated with cardiac function and regulation of the electrophysiological properties of the myocardium. 3 The 4.1 protein family is also part of the spectrin-associated cytoskeleton. It promotes the interaction between spectrin and F-actin and, thus, membrane stability. 2 In mammals, the 4 genes, EPB41, EPB41L1, EPB41L2, and EPB41L3, encode proteins 4.1R, 4.1G, 4.1N, and 4.1B. mRNA transcripts from all 4 genes are found in mouse myocardium. 4 All 4.1 proteins have a FERM membranebinding domain, a spectrin-actin binding (SAB) domain, and a C-terminal domain. 2 A FERM-adjacent domain regulates the activities of both FERM and SAB domains. 5 The FERM and C-terminal domains bind to membrane proteins, 6 whereas the SAB domain binds the spectrin-actin cytoskeleton. 7 Multiple ion channels, pumps, and exc...

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“…Erythrocyte protein 4.1 also enhances the spectrin-actin interaction of many nonerythroid spectrins, including mammalian brain spectrin [Burns et al, 1983;Lin et al, 1983;Coleman et a]., 1987,19891, and avian brain spectrin [Coleman et al, 1987,19891. Ultrastructural studies have localized actin and protein 4.1 binding to the end of the spectrin molecule opposite the oligomerization site [Tyler et al, 1979, 19801.…”

Section: Spectrin-filament Linkages Spectrin-protein 41 -Actinmentioning

confidence: 99%

Functional diversity among spectrin isoforms

Coleman

Fishkind

Mooseker

et al. 1989

Cell Motil. Cytoskeleton

115

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The purpose of this review on spectrin is to examine the functional properties of this ubiquitous family of membrane skeletal proteins. Major topics include spectrin-membrane linkages, spectrin-filament linkages, the subcellular localization of spectrins in various cell types and a discussion of major functional differences between erythroid and nonerythroid spectrins. This includes a summary of studies from our own laboratories on the functional and structural comparison of avian spectrin isoforms which are comprised of a common alpha subunit and a tissue-specific beta subunit. Consequently, the observed differences among these spectrins can be assigned to differences in the properties of the beta subunits.

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Properties of brain spectrin (fodrin)

Cited by 57 publications

References 22 publications

Primary structure of the brain alpha-spectrin [published erratum appears in J Cell Biol 1989 Mar;108(3):following 1175]

Primary structure of the brain alpha-spectrin [published erratum appears in J Cell Biol 1989 Mar;108(3):following 1175]

Cytoskeletal Protein 4.1R Affects Repolarization and Regulates Calcium Handling in the Heart

Functional diversity among spectrin isoforms

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