Spatio-Temporal Regulation of Rac1 Localization and Lamellipodia Dynamics during Epithelial Cell-Cell Adhesion

Ehrlich, Jason S.; Hansen, Marc D.H.; Nelson, W. James

doi:10.1016/s1534-5807(02)00216-2

Cited by 322 publications

(318 citation statements)

References 50 publications

(65 reference statements)

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“…The Rac GTPase has been implicated in the formation of adherens junctions (26,27). In agreement with previous findings (27), we observed that Rac was activated by 5 min of cadherin engagement (Fig.…”

Section: Abl Kinases Regulate Rac Activation In Response Tosupporting

confidence: 93%

Abl tyrosine kinases regulate cell–cell adhesion through Rho GTPases

Zandy

Playford

Pendergast

2007

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

118

132

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Section: Abl Kinases Regulate Rac Activation In Response Tosupporting

confidence: 93%

Abl tyrosine kinases regulate cell–cell adhesion through Rho GTPases

Zandy

Playford

Pendergast

2007

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

118

132

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“…3B and Movie S2). This effect mimicked the decrease in lamellipodia activity at both cell-cell contacting and noncontacting membranes observed during intercellular adhesion between MDCK cells (11).…”

Section: Resultssupporting

confidence: 62%

“…ECM-based cell migration results from the transformation of actomyosin cytoskeleton activity into cell translocation by force transmission to the ECM through integrin-based Focal Adhesions (FAs) (10). Crosstalk between intercellular adhesion and cell migration is suggested from observations of spatiotemporal regulation of lamellipodia activity upon cell-cell contact (11) and redistribution of FAs away from cell-cell contacts during initial cell-cell adhesion (12). However, most of our knowledge about ECM-based cell migration comes from studies of individual cells.…”

mentioning

confidence: 99%

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.

202

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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“…ELF rescues E-cadherin/b-catenin substrate-independent cell-cell adhesion To define the abnormalities associated in the formation and organization of individual cell-cell contacts in elf þ /À /Smad4 þ /À mutants, we used functional quantitative assays of cell-cell adhesion (Ehrlich et al, 2002) using gastric cells derived from the elf þ /À /Smad4 þ /À mice. Effects on populations of cells were quantified by a hanging drop assay that measures the size of cell aggregates after being subjected to a shearing force (Kim et al, 2000).…”

Section: Elf Is a Localizing Protein For E-cadherin At Cell-cell Contmentioning

confidence: 99%

Critical interactions between TGF-β signaling/ELF, and E-cadherin/β-catenin mediated tumor suppression

Katuri

Tang

et al. 2006

Oncogene

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Inactivation of the transforming growth factor-b (TGF-b) pathway occurs often in malignancies of the gastrointestinal (GI) system. However, only a fraction of sporadic GI tumors exhibit inactivating mutations in early stages of cancer formation, suggesting that other mechanisms play a critical role in the inactivation of this pathway. Here, we show a wide range of GI tumors, including those of the stomach, liver and colon in elf þ /À and elf þ /À /Smad4 þ /À mutant mice. We found that embryonic liver fodrin (ELF), a b-Spectrin originally identified in endodermal stem/ progenitor cells committed to foregut lineage, possesses potent antioncogenic activity and is frequently inactivated in GI cancers. Specifically, E-cadherin accumulation at cell-cell contacts and E-cadherin-b-catenin-dependent epithelial cell-cell adhesion is disrupted in elf þ /À / Smad4 þ /À mutant gastric epithelial cells, and could be rescued by ectopic expression of full-length elf, but not Smad3 or Smad4. Subcellular fractionation revealed that E-cadherin is expressed mainly at the cell membrane after TGF-b stimulation. In contrast, elf þ /À /Smad4 þ /À mutant tissues showed abnormal distribution of E-cadherin that could be rescued by overexpression of ELF but not Smad3 or Smad4. Our results identify a group of common lethal malignancies in which inactivation of TGF-b signaling, which is essential for tumor suppression, is disrupted by inactivation of the ELF adaptor protein.

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Spatio-Temporal Regulation of Rac1 Localization and Lamellipodia Dynamics during Epithelial Cell-Cell Adhesion

Cited by 322 publications

References 50 publications

Abl tyrosine kinases regulate cell–cell adhesion through Rho GTPases

Abl tyrosine kinases regulate cell–cell adhesion through Rho GTPases

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

Critical interactions between TGF-β signaling/ELF, and E-cadherin/β-catenin mediated tumor suppression

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