The Prototypical 4.1R-10-kDa Domain and the 4.1G-10-kDa Paralog Mediate Fodrin-Actin Complex Formation

Kontrogianni‐Konstantopoulos, Aikaterini; Frye, Carole S.; Benz, Edward J.; Huang, Shu-Ching

doi:10.1074/jbc.m010581200

Cited by 31 publications

(28 citation statements)

References 51 publications

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“…their function is a characteristic spacing of hydrophobic residues, mainly leucine or isoleucine (38,39). Analysis of the amino acid sequence coded by exon 5 allowed the identification of a hydrophobic region, L 26 LKRVCEHLNLL, which is significantly similar to leucine-rich NES sequences (Fig. 3A).…”

Section: Exon 5-encoded Sequence Alters the Subcellular Localizationmentioning

confidence: 98%

“…The crystal structure of the N-terminal 30-kDa domain of erythroid 4.1R comprising exon-5-encoded sequence has been determined (53). From the tertiary structure it may be inferred that the 4.1R hydrophobic sequence, L 26 LKRVCEHLNLL , adopts an ␣-helix conformation (Fig. 3D).…”

Section: Exon 5-encoded Sequence Alters the Subcellular Localizationmentioning

confidence: 99%

“…Immunological studies have detected 4.1R epitopes at different intracellular sites (14 -20). Concomitantly, the association of 4.1R with proteins localized at different intracellular sites have been reported (21)(22)(23)(24)(25)(26)(27), thus suggesting that 4.1R may be involved in many processes in nucleated cells. A possible role for 4.1R in organizing the nuclear and microtubule architecture and the mitotic spindle poles has been suggested.…”

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confidence: 99%

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An Alternative Domain Containing a Leucine-rich Sequence Regulates Nuclear Cytoplasmic Localization of Protein 4.1R

Luque¹,

Pérez-Ferreiro²,

Pérez-González³

et al. 2003

Journal of Biological Chemistry

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In red blood cells, protein 4.1 (4.1R) is an 80-kDa protein that stabilizes the spectrin-actin network and anchors it to the plasma membrane. The picture is more complex in nucleated cells, in which many 4.1R isoforms, varying in size and intracellular location, have been identified. To contribute to the characterization of signals involved in differential intracellular localization of 4.1R, we have analyzed the role the exon 5-encoded sequence plays in 4.1R distribution. We show that exon 5 encodes a leucine-rich sequence that shares key features with nuclear export signals (NESs). This sequence adopts the topology employed for NESs of other proteins and conserves two hydrophobic residues that are shown to be critical for NES function. A 4.1R isoform expressing the leucine-rich sequence binds to the export receptor CRM1 in a RanGTP-dependent fashion, whereas this does not occur in a mutant whose two conserved hydrophobic residues are substituted. These two residues are also essential for 4.1R intracellular distribution, because the 4.1R protein containing the leucine-rich sequence localizes in the cytoplasm, whereas the mutant protein predominantly accumulates in the nucleus. We hypothesize that the leucine-rich sequence in 4.1R controls distribution and concomitantly function of a specific set of 4.1R isoforms.

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Section: Exon 5-encoded Sequence Alters the Subcellular Localizationmentioning

confidence: 98%

Section: Exon 5-encoded Sequence Alters the Subcellular Localizationmentioning

confidence: 99%

mentioning

confidence: 99%

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An Alternative Domain Containing a Leucine-rich Sequence Regulates Nuclear Cytoplasmic Localization of Protein 4.1R

Luque¹,

Pérez-Ferreiro²,

Pérez-González³

et al. 2003

Journal of Biological Chemistry

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“…Through interactions with other cytoskeletal components, including F-actin and ankyrin, as well as signaling molecules such as synapsin I, membrane-associated guanylate kinases, and phospholipids, spectrins are ideally positioned to coordinate cellular responses culminating in Ca 2ϩ entry (21). Spectrins are also known to form complexes with various Ca 2ϩ regulators, including IP 3 Rs, ryanodine receptors, Na ϩ /K ϩ -ATPase, various ion channels, N-methyl-D-aspartic acid receptor subunits, and the epithelial Na ϩ channel, ENaC (23,(47)(48)(49)(50)(51), positioning them as potential critical regulators of Ca 2ϩ levels. Interactions between hTRPC4 and the spectrin cytoskeleton may also provide a functional bridge between the endoplasmic reticulum and plasma membrane, forming a mechanism for linking Ca 2ϩ release from intracellular stores with Ca 2ϩ entry through the plasma membrane.…”

Section: Discussionmentioning

confidence: 99%

The Spectrin Cytoskeleton Influences the Surface Expression and Activation of Human Transient Receptor Potential Channel 4 Channels

Odell

Helden²,

Scott

2008

Journal of Biological Chemistry

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Despite over a decade of research, only recently have the mechanisms governing transient receptor potential channel (TRPC) channel function begun to emerge, with an essential role for accessory proteins in this process. We previously identified a tyrosine phosphorylation event as critical in the plasma membrane translocation and activation of hTRPC4 channels following epidermal growth factor (EGF) receptor activation. To further characterize the signaling events underlying this process, a yeast-two hybrid screen was performed on the C terminus of hTRPC4. The intracellular C-terminal region from proline 686 to leucine 977 was used to screen a human brain cDNA library. Two members of the spectrin family, ␣II-and ␤V-spectrin, were identified as binding partners. The interaction of hTRPC4 with ␣II-spectrin and ␤V-spectrin was confirmed by glutathione S-transferase pulldown and co-immunoprecipitation experiments. Deletion analysis identified amino acids 730 -758 of hTRPC4 as critical for the interaction with this region located within a coiled-coil domain, juxtaposing the Ca 2؉ /calmodulin-and IP 3 R-binding region (CIRB domain). This region is deleted in the proposed ␦hTRPC4 splice variant form, which failed to undergo both EGF-induced membrane insertion and activation, providing a genetic mechanism for regulating channel activity. We also demonstrate that the exocytotic insertion and activation of hTRPC4 following EGF application is accompanied by dissociation from ␣II-spectrin. Furthermore, depletion of ␣II-spectrin by small interference RNA reduces the basal surface expression of ␣hTRPC4 and prevents the enhanced membrane insertion in response to EGF application. Importantly, depletion of ␣II-spectrin did not affect the expression of the ␦ variant. Taken together, these results demonstrate that a direct interaction between hTRPC4 and the spectrin cytoskeleton is involved in the regulation of hTRPC4 surface expression and activation.

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“…Western blot analysis for the human 4.1R protein was performed according to a previously described procedure (8)(9)(10).…”

Section: Extraction and Purification Of Human 41r Proteinmentioning

confidence: 99%

Interaction between protein 4.1R and spectrin heterodimers

Zhang¹,

Wang

et al. 2011

Mol Med Rep

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Abstract. Defects or deficiencies in red cell membrane skeletal proteins often undermine the integrity and stability of the plasma membrane, and consequently cause hereditary hemolytic anemias. Genetic and biochemical studies have revealed a complicated picture of the organization of the membrane skeleton, within which α-/β-spectrin heterodimers form a protein lattice. By stabilizing the red cell membrane skeleton, the erythroid protein 4.1R greatly contributes to connecting and regulating the interaction among spectrins, actin filaments and integral proteins on the plasma membrane. In this study, we demonstrated the direct interaction between 4.1R and α-/β-spectrin. The results provide novel insights into the stoichiometry of 4.1R with spectrin, and demonstrate for the first time that the binding ratio of 4.1R to spectrin heterodimers is approximately 5.

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The Prototypical 4.1R-10-kDa Domain and the 4.1G-10-kDa Paralog Mediate Fodrin-Actin Complex Formation

Cited by 31 publications

References 51 publications

An Alternative Domain Containing a Leucine-rich Sequence Regulates Nuclear Cytoplasmic Localization of Protein 4.1R

An Alternative Domain Containing a Leucine-rich Sequence Regulates Nuclear Cytoplasmic Localization of Protein 4.1R

The Spectrin Cytoskeleton Influences the Surface Expression and Activation of Human Transient Receptor Potential Channel 4 Channels

Interaction between protein 4.1R and spectrin heterodimers

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