αII-Spectrin interacts with five groups of functionally important proteins in the nucleus

Sridharan, Deepa; McMahon, Laura; Lambert, Muriel W.

doi:10.1016/j.cellbi.2006.06.005

Cited by 47 publications

(107 citation statements)

References 68 publications

(159 reference statements)

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“…Alpha spectrin is identified at the nuclear envelope [30]. More recently, Lambert and colleagues demonstrated that SpαII is involved in DNA repair in the nucleus [19,20,48,49] (Tab. 2).…”

Section: Suggested Functions In Nucleimentioning

confidence: 99%

“…SpαII is localized to multiple nuclear foci along with two DNA-repair proteins (FANCA and XPF) to which it binds directly [49]. Recent studies suggested that SpαII may play a role in a number of diverse and important processes in the nucleus [20]. It has also been reported that erythroid protein 4.1 (4.1R), originally identified as a component of the membrane-skeleton of the erythrocyte, could play an important role in organizing the nuclear architecture, mitotic spindle, and spindle poles [50][51][52].…”

Section: Suggested Functions In Nucleimentioning

confidence: 99%

“…Spectrin is generally considered to be a structural (cytoskeletal) protein involved in stabilization of cell surface membranes at sites of cell-cell contacts [17], protein sorting [9], and protein accumulation [18]. Spectrin is also involved in regulation of signal transduction pathways [12], and in the regulation of DNA repair [19,20]. However, studies of gene knock-outs in model organisms suggest that these genes are not essential for fundamental cellular function, but act at the level of integration of cells into tissues, and, thus, mutations may be compatible with survival but impart impaired physiological function, and are therefore candidates to cause disease in humans [14].…”

Section: Introductionmentioning

confidence: 99%

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Brain proteins interacting with the tetramerization region of non-erythroid alpha spectrin

Fung

2007

Cellular and Molecular Biology Letters

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Abstract:The N-terminal region of non-erythroid alpha spectrin (SpαII) is responsible for interacting with its binding partner, beta spectrin, to form functional spectrin tetramers. We used a yeast-two-hybrid system, with an N-terminal segment of alpha spectrin representing the functional tetramerization site, as a bait to screen human brain c-DNA library for proteins that interact with the alpha spectrin segment. In addition to several beta spectrin isoforms, we identified 14 proteins that interact with SpαII. Seven of the 14 were matched to 6 known proteins: Duo protein, Lysyl-tRNA synthetase, TBP associated factor 1, two isoforms (b and c) of a protein kinase A interacting protein and Zinc finger protein 333 (2 different segments). Four of the 6 proteins are located primarily in the nucleus, suggesting that spectrin plays important roles in nuclear functions. The remaining 7 proteins were unknown to the protein data base. Structural predictions show that many of the 14 proteins consist of a large portion of unstructured regions, suggesting that many of these proteins fold into a rather flexible conformation. It is interesting to note that all but 3 of the 14 proteins are predicted to consist of one to four coiled coils (amphiphilic helices). A mutation in SpαII, V22D, which interferes with the coiled coil bundling of SpαII with beta spectrin, also affects SpαII interaction with Duo protein, TBP associated factor 1 and Lysyl-tRNA synthetase, suggesting that they may compete with beta spectrin for interaction with SpαII. Future structural and functional studies of these proteins to provide interaction mechanisms will no doubt lead to a better understanding of brain physiology and pathophysiology.

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“…Alpha spectrin is identified at the nuclear envelope [30]. More recently, Lambert and colleagues demonstrated that SpαII is involved in DNA repair in the nucleus [19,20,48,49] (Tab. 2).…”

Section: Suggested Functions In Nucleimentioning

confidence: 99%

Section: Suggested Functions In Nucleimentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Brain proteins interacting with the tetramerization region of non-erythroid alpha spectrin

Fung

2007

Cellular and Molecular Biology Letters

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“…Formation of these complexes could be mediated through interactions with actin, II-spectrin or microtubules that bind 4.1R; II-spectrin has been detected in several emerin complexes purified from HeLa cells (Holaska and Wilson, 2007) and emerin has been identified in II-spectrin complexes (Sridharan et al, 2006). These are particularly attractive models, with precedent in erythrocytes, where 4.1R forms multiprotein complexes ultimately crucial for mature erythrocyte morphology and mechanical properties.…”

Section: Discussionmentioning

confidence: 99%

Structural protein 4.1R is integrally involved in nuclear envelope protein localization, centrosome–nucleus association and transcriptional signaling

Meyer

Almendrala

et al. 2011

Journal of Cell Science

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SummaryThe multifunctional structural protein 4.1R is required for assembly and maintenance of functional nuclei but its nuclear roles are unidentified. 4.1R localizes within nuclei, at the nuclear envelope, and in cytoplasm. Here we show that 4.1R, the nuclear envelope protein emerin and the intermediate filament protein lamin A/C co-immunoprecipitate, and that 4.1R-specific depletion in human cells by RNA interference produces nuclear dysmorphology and selective mislocalization of proteins from several nuclear subcompartments. Such 4.1R-deficiency causes emerin to partially redistribute into the cytoplasm, whereas lamin A/C is disorganized at nuclear rims and displaced from nucleoplasmic foci. The nuclear envelope protein MAN1, nuclear pore proteins Tpr and Nup62, and nucleoplasmic proteins NuMA and LAP2 also have aberrant distributions, but lamin B and LAP2 have normal localizations. 4.1R-deficient mouse embryonic fibroblasts show a similar phenotype. We determined the functional effects of 4.1R-deficiency that reflect disruption of the association of 4.1R with emerin and A-type lamin: increased nucleus-centrosome distances, increased -catenin signaling, and relocalization of -catenin from the plasma membrane to the nucleus. Furthermore, emerin-and lamin-A/C-null cells have decreased nuclear 4.1R. Our data provide evidence that 4.1R has important functional interactions with emerin and A-type lamin that impact upon nuclear architecture, centrosome-nuclear envelope association and the regulation of -catenin transcriptional co-activator activity that is dependent on -catenin nuclear export.

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“…Spectrin is involved in the formation and maintenance of plasma membranes at sites of cell-cell contacts [5], protein sorting and accumulation [6], interactions with structural and regulatory proteins [7], regulation of signal transduction pathways [8], and regulation of DNA repair [9]. Non-erythroid spectrin (spectrin II), also referred to as brain spectrin [10], calspectin [11], or fodrin [12], is found in neuronal axons [13], whereas erythroid spectrin (spectrin I) is confined to neuronal cell bodies and dendrites, and some glial cells [14].…”

Section: Introductionmentioning

confidence: 99%

Non-erythroid beta spectrin interacting proteins and their effects on spectrin tetramerization

Sevinc

Fung

2011

Cellular and Molecular Biology Letters

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With yeast two-hybrid methods, we used a C-terminal fragment (residues 1697-2145) of non-erythroid beta spectrin (βII-C), including the region involved in the association with alpha spectrin to form tetramers, as the bait to screen a human brain cDNA library to identify proteins interacting with βII-C. We applied stringent selection steps to eliminate false positives and identified 17 proteins that interacted with βII-C (IPβII-C s). The proteins include a fragment (residues 38-284) of “THAP domain containing, apoptosis associated protein 3, isoform CRA g”, “glioma tumor suppressor candidate region gene 2” (residues 1-478), a fragment (residues 74-442) of septin 8 isoform c, a fragment (residues 704-953) of “coatomer protein complex, subunit beta 1, a fragment (residues 146-614) of zinc-finger protein 251, and a fragment (residues 284-435) of syntaxin binding protein 1. We used yeast three-hybrid system to determine the effects of these βII-C interacting proteins as well as of 7 proteins previously identified to interact with the tetramerization region of non-erythroid alpha spectrin (IPαII-N s) [1] on spectrin tetramer formation. The results showed that 3 IPβII-C s were able to bind βII-C even in the presence of αII-N, and 4 IPαII-N s were able to bind αII-N in the presence of βII-C. We also found that the syntaxin binding protein 1 fragment abolished αII-N and βII-C interaction, suggesting that this protein may inhibit or regulate non-erythroid spectrin tetramer formation.

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αII-Spectrin interacts with five groups of functionally important proteins in the nucleus

Cited by 47 publications

References 68 publications

Brain proteins interacting with the tetramerization region of non-erythroid alpha spectrin

Brain proteins interacting with the tetramerization region of non-erythroid alpha spectrin

Structural protein 4.1R is integrally involved in nuclear envelope protein localization, centrosome–nucleus association and transcriptional signaling

Non-erythroid beta spectrin interacting proteins and their effects on spectrin tetramerization

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