E-cadherin-mediated Cell-Cell Attachment Activates Cdc42

Kim, Stella H.; Li, Zhigang; Sacks, David B.

doi:10.1074/jbc.m003430200

Cited by 203 publications

(167 citation statements)

References 49 publications

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“…The effects of constitutively active Cdc42 in MDCK cells resemble those of activated Rac1, although the interdigitation of the lateral membranes is much less pronounced (Kodama et al 1999). Similar to Rac, Cdc42 is activated by E-cadherin-mediated cell-cell contact in a PI3K-dependent fashion (Kim et al 2000) and Cdc42 activity is necessary for E-cadherin-dependent cell interactions (Fukata et al 1999). It is interesting to note, however, that in Drosophila expression of a dominant negative version of DCdc42 does not have any significant effect on cell-cell junctions in the developing wing disc epithelium .…”

Section: Adherens Junctionsmentioning

confidence: 88%

Role of Rho family GTPases in epithelial morphogenesis

Aelst¹,

Symons²

2002

Genes Dev.

213

184

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Section: Adherens Junctionsmentioning

confidence: 88%

Role of Rho family GTPases in epithelial morphogenesis

Aelst¹,

Symons²

2002

Genes Dev.

213

184

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“…We focused on Cdc42 activity, which is largely associated with filopodia formation (and early stages of cell-cell adhesion) (7,9,10), and Rac1 activity, which is associated with lamellipodial activity (and intermediate stages of cell-cell adhesion) (15,16,50). We did not investigate the role of RhoA because its activity is important in late stages of cell-cell adhesion and compaction (15).…”

Section: Resultsmentioning

confidence: 99%

“…Adhesion is initiated when filopodia from opposing cells come into contact with one another (7,8), and this process is regulated by Cdc42 activity (9,10) and formin-dependent actin polymerization (11)(12)(13)(14). Intermediate stages of cell-cell contact formation involve lateral expansion of the contact by Rac1-induced and Arp2/3-dependent lamellipodial activity (15,16).…”

mentioning

confidence: 99%

Changes in E-cadherin rigidity sensing regulate cell adhesion

Collins

Denisin

Pruitt

et al. 2017

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

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Mechanical cues are sensed and transduced by cell adhesion complexes to regulate diverse cell behaviors. Extracellular matrix (ECM) rigidity sensing by integrin adhesions has been well studied, but rigidity sensing by cadherins during cell adhesion is largely unexplored. Using mechanically tunable polyacrylamide (PA) gels functionalized with the extracellular domain of E-cadherin (Ecad-Fc), we showed that E-cadherin-dependent epithelial cell adhesion was sensitive to changes in PA gel elastic modulus that produced striking differences in cell morphology, actin organization, and membrane dynamics. Traction force microscopy (TFM) revealed that cells produced the greatest tractions at the cell periphery, where distinct types of actin-based membrane protrusions formed. Cells responded to substrate rigidity by reorganizing the distribution and size of hightraction-stress regions at the cell periphery. Differences in adhesion and protrusion dynamics were mediated by balancing the activities of specific signaling molecules. Cell adhesion to a 30-kPa Ecad-Fc PA gel required Cdc42-and formin-dependent filopodia formation, whereas adhesion to a 60-kPa Ecad-Fc PA gel induced Arp2/3-dependent lamellipodial protrusions. A quantitative 3D cell-cell adhesion assay and live cell imaging of cell-cell contact formation revealed that inhibition of Cdc42, formin, and Arp2/3 activities blocked the initiation, but not the maintenance of established cell-cell adhesions. These results indicate that the same signaling molecules activated by E-cadherin rigidity sensing on PA gels contribute to actin organization and membrane dynamics during cell-cell adhesion. We hypothesize that a transition in the stiffness of E-cadherin homotypic interactions regulates actin and membrane dynamics during initial stages of cellcell adhesion.C ell adhesion is essential for tissue structure and function. Cells use specialized types of adhesions to interact with the surrounding environment, including integrin-based focal adhesions at cell-extracellular matrix (cell-ECM) contacts and cadherin-based adhesions at cell-cell contacts (1). Integrins bind to the ECM and intracellular proteins that link to the actin cytoskeleton and important signaling pathways (2). Similarly, cadherins regulate cellcell recognition and adhesion (3) and, through cytoplasmic adaptor proteins (catenins, vinculin) (4, 5), also link to the actin cytoskeleton and other proteins with signaling and scaffolding functions (6).Initiation of cell-cell adhesion requires significant reorganization of the actin cytoskeleton and is tightly controlled by the activities of actin nucleating proteins and Rho GTPases. Adhesion is initiated when filopodia from opposing cells come into contact with one another (7,8), and this process is regulated by Cdc42 activity (9, 10) and formin-dependent actin polymerization (11)(12)(13)(14). Intermediate stages of cell-cell contact formation involve lateral expansion of the contact by Rac1-induced and Arp2/3-dependent lamellipodial activity (15, 16). Finally, com...

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“…Immunocytochemistry was performed essentially as described [11,27] with a few modifications. Briefly, cells were washed twice with phosphate-buffered saline (PBS) and incubated in 4% paraformaldehyde-PBS for 20 min at 4 °C.…”

Section: Immunofluorescence Staining and Confocal Microscopymentioning

confidence: 99%

Multiple proteins mediate IQGAP1-stimulated cell migration

Mataraza

Jeong

et al. 2007

Cellular Signalling

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Cell migration, a highly complex physiological phenomenon that requires the co-ordinated and tightly regulated function of several proteins, is mediated by a number of signalling pathways. Elucidation of the molecular mechanisms of cell migration impacts our comprehension of numerous cell functions, ranging from development and immune surveillance to angiogenesis and metastasis. The scaffold protein IQGAP1, which binds multiple proteins and regulates their functions, promotes cell motility. Many of the IQGAP1 binding proteins have been implicated in cell migration. In this study, we employed a multifaceted strategy to identify proteins that contribute to IQGAP1-stimulated cell migration. Using specific IQGAP1 point mutant constructs, an interaction with actin was shown to be essential for IQGAP1 to increase cell migration. In contrast, eliminating the binding of Ca 2+ / calmodulin, but not Ca 2+ -free calmodulin, augmented the ability of IQGAP1 to stimulate cell migration. Consistent with these findings, selective inhibition of calmodulin function at the plasma membrane with a specific peptide inhibitor enhanced cell migration mediated by IQGAP1. Interestingly, immunofluorescence staining and confocal microscopy suggest that localization of Cdc42 at the leading edge is not necessary for maximal migration of epithelial cells. Coupled with the observations that Cdc42 and Rac1 contribute to IQGAP1-stimulated cell migration, these data suggest that IQGAP1 serves as a junction to integrate multiple signalling molecules to facilitate cell migration.

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E-cadherin-mediated Cell-Cell Attachment Activates Cdc42

Cited by 203 publications

References 49 publications

Role of Rho family GTPases in epithelial morphogenesis

Role of Rho family GTPases in epithelial morphogenesis

Changes in E-cadherin rigidity sensing regulate cell adhesion

Multiple proteins mediate IQGAP1-stimulated cell migration

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