Vinculin is an Essential Component for Normal Myofibrillar Arrangement in Fetal Mouse Cardiac Myocytes

Shiraishi, Isao; Simpson, David G.; Carver, Wayne; Price, Robert L.; Hirozane, Toshiro; Terracio, Louis; Borg, Thomas K.

doi:10.1006/jmcc.1997.0438

Cited by 46 publications

(27 citation statements)

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“…siRNA depletion of vinculin led to a loss of 75% of total vinculin content and 50% of vinculin from FAs (Fig. S2); excess cytoplasmic vinculin may buffer vinculin depletion at FAs, as observed by others (27,28). At this level of vinculin depletion, lamellipodia activity increased slightly over collagenIV stripes on collagenIV:EcadFc surfaces (Fig.…”

Section: Resultsmentioning

confidence: 55%

Regulation of cell motile behavior by crosstalk between cadherin- and integrin-mediated adhesions

Borghi¹,

Lowndes²,

Maruthamuthu

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

206

169

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During normal development and in disease, cohesive tissues undergo rearrangements that require integration of signals from cell adhesions to neighboring cells and to the extracellular matrix (ECM). How a range of cell behaviors is coordinated by these different adhesion complexes is unknown. To analyze epithelial cell motile behavior in response to combinations of cell-ECM and cell-cell adhesion cues, we took a reductionist approach at the single-cell scale by using unique, functionalized micropatterned surfaces comprising alternating stripes of ECM (collagenIV) and adjustable amounts of E-cadherin-Fc (EcadFc). On these surfaces, individual cells spatially segregated integrin-and cadherin-based complexes between collagenIV and EcadFc surfaces, respectively. Cell migration required collagenIV and did not occur on surfaces functionalized with only EcadFc. However, E-cadherin adhesion dampened lamellipodia activity on both collagenIV and EcadFc surfaces and biased the direction of cell migration without affecting the migration rate, all in an EcadFc concentration-dependent manner. Traction force microscopy showed that spatial confinement of integrin-based adhesions to collagenIV stripes induced anisotropic cell traction on collagenIV and migration directional bias. Selective depletion of different pools of αE-catenin, an E-cadherin and actin binding protein, identified a membrane-associated pool required for E-cadherin-mediated adhesion and down-regulation of lamellipodia activity and a cytosolic pool that down-regulated the migration rate in an E-cadherin adhesion-independent manner. These results demonstrate that there is crosstalk between E-cadherin-and integrin-based adhesion complexes and that E-cadherin regulates lamellipodia activity and cell migration directionality, but not cell migration rate.D uring development, cohesive tissues exhibit extensive rearrangements that range from en masse migration, such as in wound healing (1), to complex local cell rearrangements, such as cell intercalation (2). In extreme cases in development (3) and in diseases such as metastatic cancers (4), tissue cohesion is lost and single-cell migration enabled, which results in cells populating distant sites. These morphogenetic processes reveal the importance of a fine coregulation, or crosstalk, between tissue cohesion (cadherin-based cell-cell adhesion) and cell migration [integrinbased extracellular matrix (ECM) adhesion] in the maintenance of tissue integrity and function.Interest in the crosstalk between cell-cell adhesion and cell migration dates back to the pioneering studies of Abercrombie and Heaysman in the 1950s (5, 6) and even earlier (7). Abercrombie coined the term "contact inhibition" to describe how cell-cell interactions between fibroblasts initially inhibited and then redirected their migration. Whether cell-cell contact inhibition of cell migration results from cell-cell contact-dependent spatial redistribution or down-regulation of the cell migration machinery, or both remains unknown.A major component of inte...

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Section: Resultsmentioning

confidence: 55%

Regulation of cell motile behavior by crosstalk between cadherin- and integrin-mediated adhesions

Borghi¹,

Lowndes²,

Maruthamuthu

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

206

169

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“…Previous studies have indicated that ECM components play an important role in assembly and/or maintenance of myocyte cytoarchitecture (Hilenski et al, 1992; Imanaka-Yoshida et al, 1999; Shiraishi et al, 1997). In addition, it has been proposed that focal adhesions might serve as nucleation sites for the assembly of myofibrils (Lin et al, 1989).…”

Section: Cell-ecm Interactions Appear Normal In N-cadherindeficient Mmentioning

confidence: 99%

Cadherin-mediated adhesion is essential for myofibril continuity across the plasma membrane but not for assembly of the contractile apparatus

Luo

Radice

2003

Journal of Cell Science

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The strong coordinated contraction of heart muscle is dependent on the correct alignment and connection of the myofibrils across the plasma membrane. Previous studies indicate that N-cadherin is involved in cardiac myocyte adhesion and myofibrillogenesis. To investigate whether N-cadherin is specifically required for normal myocyte structure and function, we cultured myocytes from wild-type, N-cadherin-null and mutant embryos expressing the epithelial cadherin E-cadherin. In contrast to previous studies in chicken using N-cadherin-perturbing antibodies, our in vitro studies with mouse cells demonstrate that N-cadherin is not required for myofibrillogenesis, but is critical for myofibril organization. That is, N-cadherin-deficient myocytes beat and myofibrils were well formed; however, alignment of the myofibrils through regions of cell-cell contact was lost, resulting in their random orientation. Gap junctions were perturbed in the N-cadherin-null myocytes. By contrast, focal contacts appeared normal in the mutant cells. Furthermore,E-cadherin restored normal cell morphology and behavior to the N-cadherin-deficient myocytes, including proper alignment of the myofibrils. We conclude that a different adhesive system, most probably integrin, is responsible for myofibrillogenesis in the N-cadherin-null myocytes.

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“…It is highly expressed at costameres and intercalated discs and has been shown to be important for the determination of cell shape as well as ordered assembly and alignment of cardiac myofibrils (Shiraishi et al, 1997). Global deletion of the mouse Vcl gene causes embryonic growth retardation with lethality by E10.…”

Section: Introductionmentioning

confidence: 99%

Vinculin directly binds zonula occludens-1 and is essential for stabilizing connexin 43 containing gap junctions in cardiac Myocytes

Zemljic-Harpf

Godoy

Platoshyn

et al. 2014

Journal of Cell Science

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Vinculin (Vcl) links actin filaments to integrin-and cadherin-based cellular junctions. Zonula occludens-1 (ZO-1, also known as TJP1) binds connexin-43 (Cx43, also known as GJA1), cadherin and actin. Vcl and ZO-1 anchor the actin cytoskeleton to the sarcolemma. Given that loss of Vcl from cardiomyocytes causes maldistribution of Cx43 and predisposes cardiomyocyte-specific Vcl-knockout mice with preserved heart function to arrhythmia and sudden death, we hypothesized that Vcl and ZO-1 interact and that loss of this interaction destabilizes gap junctions. We found that Vcl, Cx43 and ZO-1 colocalized at the intercalated disc. Loss of cardiomyocyte Vcl caused parallel loss of ZO-1 from intercalated dics. Vcl coimmunoprecipitated Cx43 and ZO-1, and directly bound ZO-1 in yeast two-hybrid studies. Excision of the Vcl gene in neonatal mouse cardiomyocytes caused a reduction in the amount of Vcl mRNA transcript and protein expression leading to (1) decreased protein expression of Cx43, ZO-1, talin, and b1D-integrin, (2) reduced PI3K activation, (3) increased activation of Akt, Erk1 and Erk2, and (4) cardiomyocyte necrosis. In summary, this is the first study showing a direct interaction between Vcl and ZO-1 and illustrates how Vcl plays a crucial role in stabilizing gap junctions and myocyte integrity.

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Vinculin is an Essential Component for Normal Myofibrillar Arrangement in Fetal Mouse Cardiac Myocytes

Cited by 46 publications

References 0 publications

Regulation of cell motile behavior by crosstalk between cadherin- and integrin-mediated adhesions

Regulation of cell motile behavior by crosstalk between cadherin- and integrin-mediated adhesions

Cadherin-mediated adhesion is essential for myofibril continuity across the plasma membrane but not for assembly of the contractile apparatus

Vinculin directly binds zonula occludens-1 and is essential for stabilizing connexin 43 containing gap junctions in cardiac Myocytes

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