An interaction between zyxin and alpha-actinin.

Crawford, Aaron W.; Michelsen, James W.; Beckerle, Mary C.

doi:10.1083/jcb.116.6.1381

Cited by 238 publications

(191 citation statements)

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“…The hypothesis was that their variable association with focal adhesions and stress fibers, as shown in previous studies (Crawford et al, 1992;Rottner et al, 2001), may reflect different states of focal adhesions in responses to mechanical signals and/or cell migration. We observed two discrete patterns of the distribution of these proteins near focal adhesions in the lamella region of NIH3T3 cells.…”

Section: Retrograde Flux Of Zyxin At Focal Adhesions In Relation To Cmentioning

confidence: 99%

“…Several proteins, including zyxin and vasodilator-stimulated phosphoprotein (VASP), are known to localize to a variable extent at focal adhesions (Crawford et al, 1992;Rottner et al, 2001), or to shuttle between focal adhesions and the nucleus (Nix and Beckerle, 1997;Aplin and Juliano, 2001). Recent studies further indicated that mechanical stimulation can induce the change in distribution of zyxin from focal adhesions to either actin stress fibers in cultured fibroblasts (Yoshigi et al, 2005), or the nucleus of vascular smooth muscle cells (Cattaruzza et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

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Retrograde Fluxes of Focal Adhesion Proteins in Response to Cell Migration and Mechanical Signals

Guo

Wang

2007

MBoC

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Recent studies suggest that mechanical signals mediated by the extracellular matrix play an essential role in various physiological and pathological processes; yet, how cells respond to mechanical stimuli remains elusive. Using live cell fluorescence imaging, we found that actin filaments, in association with a number of focal adhesion proteins, including zyxin and vasodilator-stimulated phosphoprotein, undergo retrograde fluxes at focal adhesions in the lamella region. This flux is inversely related to cell migration, such that it is amplified in fibroblasts immobilized on micropatterned islands. In addition, the flux is regulated by mechanical signals, including stretching forces applied to flexible substrates and substrate stiffness. Conditions favoring the flux share the common feature of causing large retrograde displacements of the interior actin cytoskeleton relative to the substrate anchorage site, which may function as a switch translating mechanical input into chemical signals, such as tyrosine phosphorylation. In turn, the stimulation of actin flux at focal adhesions may function as part of a feedback mechanism, regulating structural assembly and force production in relation to cell migration and mechanical load. The retrograde transport of associated focal adhesion proteins may play additional roles in delivering signals from focal adhesions to the interior of the cell. INTRODUCTIONRecent studies suggest that mechanosensing is involved in several physiological processes, including embryogenesis (Newman and Comper, 1990;Beloussov et al., 1994) and wound healing (Hinz et al., 2001;Tomasek et al., 2002), and in pathological processes such as fibrosis and carcinogenesis (Paszek et al., 2005). Adherent cells seem capable of both responding to applied mechanical forces (Tzima et al., 2005) and applying contractile forces to probe mechanical properties of the environment (Discher et al., 2005). The downstream responses include changes in migration (Pelham and Wang, 1997;Sheetz et al., 1998;Lo et al., 2000), cell-cell interactions (Guo et al., 2006), proliferation (Wang et al., 2000Nelson et al., 2005), differentiation (Engler et al., 2004(Engler et al., , 2006, and apoptosis . For cultured adherent cells, focal adhesions are thought to mediate mechanosensing through integrin-mediated anchorage to the extracellular matrix (Larsen et al., 2006). The molecular repertoire of focal adhesions includes Ͼ100 adaptor and signaling proteins (Bershadsky et al., 2006), in addition to associated actomyosin bundles that provide mechanical forces for probing the environment (Choquet et al., 1997), inside-out signaling (Chrzanowska-Wodnicka and Burridge, 1996;Schwartz and Ginsberg, 2002), and cell migration (Ridley et al., 2003). However, few details are available concerning how these components work in concert to generate the responses to mechanical signals.Several aspects have emerged recently as the key features of integrin-mediated mechanosensing. First is the increase in cortical organization and contractility in resp...

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Section: Retrograde Flux Of Zyxin At Focal Adhesions In Relation To Cmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Retrograde Fluxes of Focal Adhesion Proteins in Response to Cell Migration and Mechanical Signals

Guo

Wang

2007

MBoC

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“…Zyxin was subsequently purified from avian smooth muscle (Crawford and Beckerle, 1991) and was shown to be present in cells at low abundance relative to the major, well-characterized structural components of focal contacts: vinculin, talin, a,-actinin and actin itself. Interestingly, zyxin interacts directly with the relatively abundant cytoskeletal protein, ot-actinin, an association that may be important for localizing zyxin to particular subcellular domains, such as the ends of actin illaments (Crawford et al, 1992).…”

mentioning

confidence: 99%

Zyxin and cCRP: two interactive LIM domain proteins associated with the cytoskeleton.

Sadler

Crawford

Michelsen

et al. 1992

The Journal of Cell Biology

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335

247

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Abstract. Interaction with extraceUular matrix can trigger a variety of responses by cells including changes in specific gene expression and cell differentiation. The mechanism by which cell surface events are coupled to the transcriptional machinery is not understood, however, proteins localized at sites of cell-substratum contact are likely to function as signal transducers. We have recently purified and characterized a low abundance adhesion plaque protein called zyxin (Crawford, A. W., and M. C. Beckerle. 1991. J. Biol. Chem. 266:5847-5853; Crawford, A. W., J. W. Michelsen, and M. C. Beckerle. 1992. J. Cell Biol. 116:1381-1393. We have now isolated and sequenced zyxin cDNA and we report here that zyxin exhibits an unusual proline-rich NH2-terminus followed by three tandemly arrayed LIM domains. LIM domains have previously been identified in proteins that play important roles in transcriptional regulation and cellular differentiation. LIM domains have been proposed to coordinate metal ions and we have demonstrated by atomic absorption spectroscopy that purified zyxin binds zinc, a result consistent with the idea that zyxin has zinc fingers. In addition, we have discovered that zyxin interacts in vitro with a 23-kD protein that also exhibits LIM domains. Microsequence analysis has revealed that the 23-kD protein (or cCRP) is the chicken homologue of the human cysteine-rich protein (hCRP). By double-label indirect immunofluorescence, we found that zyxin and cCRP are extensively colocalized in chicken embryo fibroblasts, consistent with the idea that they interact in vivo. We conclude that LIM domains are zinc-binding sequences that may be involved in protein-protein interactions. The demonstration that two cytoskeletal proteins, zyxin and cCRP, share a sequence motif with proteins important for transcriptional regulation raises the possibility that zyxin and cCRP are components of a signal transduction pathway that mediates adhesion-stimulated changes in gene expression.

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“…PC12 cells were maintained in medium A (DMEM with 10% fetal bovine serum (FBS), 5% horse serum and 100 U penicillin-streptomycin) at 371C in a 5% CO 2 atmosphere, in a humidified incubator. All PC12 cells employed in the experiments are in naive but not differentiated form.…”

Section: Methodsmentioning

confidence: 99%

“…The PRD region displays docking sequences for several proteins in actin assembly and organization, and SH3 domains that are found in a number of proteins in signal transduction pathways. [1][2][3][4][5][6][7] The LIM domain is a double-zincfinger motif that presents in proteins involved in the regulation of cell proliferation and differentiation. 8,9 Zyxin shuttles between the nucleus and sites of cell adhesion in fibroblasts, and is thus an excellent candidate for relaying information between these two compartments.…”

mentioning

confidence: 99%

Akt phosphorylation of zyxin mediates its interaction with acinus-S and prevents acinus-triggered chromatin condensation

Liu

Tang

et al. 2007

Cell Death Differ

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Zyxin, a focal adhesion molecule, contains LIM domains and shuttles between the cytoplasm and the nucleus. Nuclear zyxin promotes cardiomyocyte survival, which is mediated by nuclear-activated Akt. However, the molecular mechanism of how zyxin antagonizes apoptosis remains elusive. Here, we report that zyxin binds to acinus-S, a nuclear speckle protein inducing apoptotic chromatin condensation after cleavage by caspases, and prevents its apoptotic action, which is regulated by Akt. Akt binds and phosphorylates zyxin on serine 142, leading to its association with acinus. Interestingly, 14-3-3c, but not f isoform selectively, triggers zyxin nuclear translocation, which is Akt phosphorylation dependent. Zyxin is also a substrate of caspases, but Akt phosphorylation is unable to prevent its apoptotic cleavage. Expression of zyxin S142D, a phosphorylation mimetic mutant, diminishes acinus proteolytic cleavage and chromatin condensation; by contrast, wild-type zyxin or unphosphorylated S142A mutant fails. Thus, Akt regulates zyxin/acinus complex formation in the nucleus, contributing to suppression of apoptosis. Cell Death and Differentiation (2007) Zyxin is a phosphoprotein that accumulates with integrins at cell-substratum attachment sites. It has a proline-rich domain (PRD) at the N-terminus and multiple LIM domains in Cterminal half. The PRD region displays docking sequences for several proteins in actin assembly and organization, and SH3 domains that are found in a number of proteins in signal transduction pathways. [1][2][3][4][5][6][7] The LIM domain is a double-zincfinger motif that presents in proteins involved in the regulation of cell proliferation and differentiation. 8,9 Zyxin shuttles between the nucleus and sites of cell adhesion in fibroblasts, and is thus an excellent candidate for relaying information between these two compartments. 10 Although some of zyxin family proteins, including Trip6 and Ajuba, affect nuclear transcription, 11 no definite evidence has yet demonstrated that zyxin is implicated in this process.Acinus, predominantly located in the nucleus, induces apoptotic chromatin condensation after cleavage by caspases. 12 It is cleaved at both its N-and C-termini, generating a p17 active form (amino acids (aa) 228-335), which triggers chromatin condensation. Acinus contains a region similar to the RNA recognition motif of Drosophila splicing regulator Sxl, suggesting that it is implicated in RNA metabolism. Indeed, acinus is a component of functional splicesomes. 13 Acinus is also found in the apoptosis-and splicing-associated protein (ASAP) complex, which is comprised of SAP18, RNPS1, and distinct isoforms of acinus. Addition of the complex to in vitro splicing assays inhibits RNA processing. 14 Moreover, knockdown of acinus inhibits oligonucleosomal DNA fragmentation during apoptosis. 15 Acinus is also a component of exon junction complex (EJC), which is deposited on exon-intron junctions during pre-mRNA splicing, and stimulates gene expression at the RNA level. 16 Recently, we show that ...

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An interaction between zyxin and alpha-actinin.

Cited by 238 publications

References 53 publications

Retrograde Fluxes of Focal Adhesion Proteins in Response to Cell Migration and Mechanical Signals

Retrograde Fluxes of Focal Adhesion Proteins in Response to Cell Migration and Mechanical Signals

Zyxin and cCRP: two interactive LIM domain proteins associated with the cytoskeleton.

Akt phosphorylation of zyxin mediates its interaction with acinus-S and prevents acinus-triggered chromatin condensation

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