SH3 domain of spectrin participates in the activation of Rac in specialized calpain-induced integrin signaling complexes

Białkowska, Katarzyna; Saido, Takaomi C.; Fox, Joan E.B.

doi:10.1242/jcs.01625

Cited by 36 publications

(38 citation statements)

References 67 publications

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“…The tyrosine phosphorylation of spectrin blocks its cleavage by calpain (Nicolas et al, 2002;Nedrelow et al, 2003), an effect also modulated by Ca 2+ and calmodulin (Harris and Morrow, 1990). Spectrin participates in the activation of the Rho GTPase Rac, and overexpression of the aII-spectrin SH3 domain inhibits Rac1 activation, actin filament formation, and cell spreading in cultured cells (Bialkowska et al, 2005). Interestingly, actin and Rac1 have also been implicated in the regulation of neuronal polarity and axon formation via the WAVE complex (Tahirovic et al, 2010), and the loss of Rac1 in neural crest cells leads to severe craniofacial and cardiovascular malformations (Thomas et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

Cell organization, growth, and neural and cardiac development require αII-spectrin

Stankewich

Cianci

Stabach

et al. 2011

Journal of Cell Science

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SummarySpectrin a2 (aII-spectrin) is a scaffolding protein encoded by the Spna2 gene and constitutively expressed in most tissues. Exon trapping of Spna2 in C57BL/6 mice allowed targeted disruption of aII-spectrin. Heterozygous animals displayed no phenotype by 2 years of age. Homozygous deletion of Spna2 was embryonic lethal at embryonic day 12.5 to 16.5 with retarded intrauterine growth, and craniofacial, neural tube and cardiac anomalies. The loss of aII-spectrin did not alter the levels of aI-or bI-spectrin, or the transcriptional levels of any b-spectrin or any ankyrin, but secondarily reduced by about 80% the steady state protein levels of bII-and bIII-spectrin. Residual bII-and bIII-spectrin and ankyrins B and G were concentrated at the apical membrane of bronchial and renal epithelial cells, without impacting cell morphology. Neuroepithelial cells in the developing brain were more concentrated and more proliferative in the ventricular zone than normal; axon formation was also impaired. Embryonic fibroblasts cultured on fibronectin from E14.5 (Spna2 2/2 ) animals displayed impaired growth and spreading, a spiky morphology, and sparse lamellipodia without cortical actin. These data indicate that the spectrin-ankyrin scaffold is crucial in vertebrates for cell spreading, tissue patterning and organ development, particularly in the developing brain and heart, but is not required for cell viability.

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Section: Discussionmentioning

confidence: 99%

Cell organization, growth, and neural and cardiac development require αII-spectrin

Stankewich

Cianci

Stabach

et al. 2011

Journal of Cell Science

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“…Now, Spectrins are recognized as a large class of proteins ubiquitously expressed during development. The Spectrin proteins organize an extended protein network just below the plasma membrane by linking different actin fibers and many other proteins by numerous interaction motifs, such as the SH3 domain in ␣-Spectrin (␣-Spec) (Bialkowska et al, 2005;Nedrelow et al, 2003). Furthermore, a pleckstrin-homology (PH) domain in ␤-Spectrin (␤-Spec) allows its direct binding to membrane lipids (Williams et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Distinct functions of α-Spectrin and β-Spectrin during axonal pathfinding

Hülsmeier¹,

Pielage²,

Rickert

et al. 2007

Development

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Cell-shape changes during development require a precise coupling of the cytoskeleton with proteins situated in the plasma membrane. Important elements controlling the shape of cells are the Spectrin proteins that are expressed as a subcortical cytoskeletal meshwork linking specific membrane receptors with F-actin fibers. Here, we demonstrate that Drosophila karussell mutations affect ␤-spectrin and lead to distinct axonal patterning defects in the embryonic CNS. karussell mutants display a slitsensitive axonal phenotype characterized by axonal looping in stage-13 embryos. Further analyses of individual, labeled neuroblast lineages revealed abnormally structured growth cones in these animals. Cell-type-specific rescue experiments demonstrate that ␤-Spectrin is required autonomously and non-autonomously in cortical neurons to allow normal axonal patterning. Within the cell, ␤-Spectrin is associated with ␣-Spectrin. We show that expression of the two genes is tightly regulated by post-translational mechanisms. Loss of ␤-Spectrin significantly reduces levels of neuronal ␣-Spectrin expression, whereas gain of ␤-Spectrin leads to an increase in ␣-Spectrin protein expression. Because the loss of ␣-spectrin does not result in an embryonic nervous system phenotype, ␤-Spectrin appears to act at least partially independent of ␣-Spectrin to control axonal patterning.

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“…Another study focuses on the spectrin  subunit SH3-homology domain. Spectrins with SH3 domains may participate in activation of Rac and Rho GTPase activities [33]. Thus, overexpressing the spectrin SH3 domain protein may inhibit Rac and actin fiber formation, thus affecting cell stretching.…”

Section: Spectrin-dependent Cell Adhesion and Spreadingmentioning

confidence: 99%

Spectrin: Structure, function and disease

Zhang

Zhao

et al. 2013

Sci. China Life Sci.

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Spectrin is a large, cytoskeletal, and heterodimeric protein composed of modular structure of and subunits, it typically contains 106 contiguous amino acid sequence motifs called "spectrin repeats". Spectrin is crucial for maintaining the stability and structure of the cell membrane and the shape of a cell. Moreover, it contributes to diverse cell functions such as cell adhesion, cell spreading, and the cell cycle. Mutations of spectrin lead to various human diseases such as hereditary hemolytic anemia, type 5 spinocerebellar ataxia, cancer, as well as others. This review focuses on recent advances in determining the structure and function of spectrin as well as its role in disease.erythrocyte, spectrin, cell cycle, mass spectrometry, disease Citation:Zhang R, Zhang C Y, Zhao Q, et al. Spectrin: Structure, function and disease.

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SH3 domain of spectrin participates in the activation of Rac in specialized calpain-induced integrin signaling complexes

Cited by 36 publications

References 67 publications

Cell organization, growth, and neural and cardiac development require αII-spectrin

Cell organization, growth, and neural and cardiac development require αII-spectrin

Distinct functions of α-Spectrin and β-Spectrin during axonal pathfinding

Spectrin: Structure, function and disease

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