Cortactin is necessary for E-cadherin–mediated contact formation and actin reorganization

Helwani, Falak; Kovács, Éva; Paterson, Andrew D.; Verma, Suzie; Ali, Radiya G.; Fanning, Alan S.; Weed, Scott A.; Yap, Alpha S.

doi:10.1083/jcb.200309034

Cited by 162 publications

(191 citation statements)

References 38 publications

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“…Moreover, CD151 expression accelerates E-cadherin-mediated intercellular adhesion by inducing Cdc42-induced filopodia extensions which form initial cell-cell contacts. Consistent with these observations, E-cadherin colocalizes and interacts with cortactin, a key regulator of actin-cytoskeleton assembly and remodeling [38].…”

Section: Epithelial Cell-cell Adhesionsupporting

confidence: 65%

EMT, the cytoskeleton, and cancer cell invasion

Yilmaz

Christofori

2009

Cancer Metastasis Rev

1,548

1,314

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The metastatic process, i.e. the dissemination of cancer cells throughout the body to seed secondary tumors at distant sites, requires cancer cells to leave the primary tumor and to acquire migratory and invasive capabilities. In a process of epithelial-mesenchymal transition (EMT), besides changing their adhesive repertoire, cancer cells employ developmental processes to gain migratory and invasive properties that involve a dramatic reorganization of the actin cytoskeleton and the concomitant formation of membrane protrusions required for invasive growth. The molecular processes underlying such cellular changes are still only poorly understood, and the various migratory organelles, including lamellipodia, filopodia, invadopodia and podosomes, still require a better functional and molecular characterization. Notably, direct experimental evidence linking the formation of migratory membrane protrusions and the process of EMT and tumor metastasis is still lacking. In this review, we have summarized recent novel insights into the molecular processes and players underlying EMT on one side and the formation of invasive membrane protrusions on the other side.

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Section: Epithelial Cell-cell Adhesionsupporting

confidence: 65%

EMT, the cytoskeleton, and cancer cell invasion

Yilmaz

Christofori

2009

Cancer Metastasis Rev

1,548

1,314

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“…It should be noted, however, that many non-specific manuevers that inhibit endocytosis can influence cadherin function by alternative mechanisms. For example, hypertonic stress induces tyrosine phosphorylation of cortactin [22], which contributes to cadherin junction integrity [23,24] (Helwani et al, unpublished). These disparate models thus remain to be resolved and warrant further investigation.…”

Section: Regulating Internalisation: the Yin And Yang Of Adhesion Andmentioning

confidence: 99%

Making and breaking contacts: the cellular biology of cadherin regulation

Yap

Crampton

Hardin

2007

Current Opinion in Cell Biology

158

159

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SummaryCadherin-mediated cell-cell interactions are dynamic processes and cadherin function is tightly regulated in response to cellular context and signaling. Ultimately, cadherin regulation is likely to reflect the interplay between a range of fundamental cellular processes, including surface organization of receptors, cytoskeletal organization and cell trafficking, that are coordinated by signaling events. In this review we focus on recent advances in understanding how interplay with membrane trafficking and other cell-cell junctions can control cadherin function. The endocytosis of cadherins, and their post-internalization fate, influence surface expression and metabolic stability of these adhesion receptors. Similarly, at the surface, components of tight junctions provide a mode of cross-talk that regulates assembly of adherens junctions.

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“…To confirm the involvement of cortactin in the regulation of EGFR recycling from early endosomes, cells were transfected with two different cortactin siRNAs (Engqvist-Goldstein et al, 2004;Helwani et al, 2004) to knock down the endogenous protein ( Figure 7B). In both experiments, EGFR recycling was recovered in cells treated with W13 (from 22 to 32%, consistent with the degree of cortactin depletion shown by Western blotting).…”

Section: Cortactin Is Involved In the Regulation Of Egf Recycling Fromentioning

confidence: 99%

“…Briefly, 19-nucleotide RNAs were chemically synthesized (Ambion, Austin, TX) based on the sequence 5Ј-AAGCUGAGGGAGAAUGUCU-UGU-3Ј (small interfering RNA; [siRNA]1) (Helwani et al, 2004) or 5Ј-GACUGGUUUUGGAGGCAAAUUUU-3Ј (siRNA2) (Engqvist-Goldstein et al, 2004). siRNA against GFP was used as a control.…”

Section: Suppression Of Cortactin Expression By Rna Interference (Rnai)mentioning

confidence: 99%

Protein Kinase Cδ and Calmodulin Regulate Epidermal Growth Factor Receptor Recycling from Early Endosomes through Arp2/3 Complex and Cortactin

Lladó

Timpson

Muga

et al. 2008

MBoC

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The intracellular trafficking of the epidermal growth factor receptor (EGFR) is regulated by a cross-talk between calmodulin (CaM) and protein kinase C␦ (PKC␦). On inhibition of CaM, PKC␦ promotes the formation of enlarged early endosomes and blocks EGFR recycling and degradation. Here, we show that PKC␦ impairs EGFR trafficking due to the formation of an F-actin coat surrounding early endosomes. The PKC␦-induced polymerization of actin is orchestrated by the Arp2/3 complex and requires the interaction of cortactin with PKC␦. Accordingly, inhibition of actin polymerization by using cytochalasin D or by overexpression of active cofilin, restored the normal morphology of the organelle and the recycling of EGFR. Similar results were obtained after down-regulation of cortactin and the sequestration of the Arp2/3 complex. Furthermore we demonstrate an interaction of cortactin with CaM and PKC␦, the latter being dependent on CaM inhibition. In summary, this study provides the first evidence that CaM and PKC␦ organize actin dynamics in the early endosomal compartment, thereby regulating the intracellular trafficking of EGFR. INTRODUCTIONCalmodulin (CaM) is a ubiquitous small calcium sensor that regulates a variety of cellular processes in a spatial and temporal manner within the cell (Toutenhoofd and Strehler, 2000). Microenvironment variations in the concentration of CaM may be critical to the control of cellular processes that involve specific and high-affinity CaM-binding proteins (Berridge et al., 2000;Carafoli, 2002;Kahl and Means, 2003).We have previously shown that CaM is crucial to the regulation of the dynamics of endosomes. In particular, in the presence of W13, a highly specific CaM antagonist, trafficking is blocked in early endosomes, thereby interfering with transport toward degradation and recycling pathways. This blockage was associated with a dramatic alteration of the morphology and size of early endosomes (Tebar et al., 2002;Lladó et al., 2004). Furthermore we showed that a cross-talk between CaM and protein kinase C␦ (PKC␦) is involved in the regulation of the budding from the early endocytic compartment (Lladó et al., 2004).Several lines of evidence implicate the actin cytoskeleton in the CaM-and PKC␦-mediated regulation of vesicular trafficking. Because actin contributes to the maintenance of organelle stability (Apodaca, 2001), swelling and morphological changes observed in response to CaM/PKC␦ activity (Lladó et al., 2004) may involve altered actin dynamics. Moreover, several CaM-binding proteins and PKC␦ substrates are also actin-binding proteins, including ␣-actinin, adducin, and myristoylated alanine-rich protein kinase C substrate (MARCKS) (Chakravarthy et al., 1999). Finally, RhoGTPases and CaM-binding proteins responsible for fusion-fission events during vesicular trafficking also depend on actin filaments for pinch-off and vesicular movement (Mayorga et al., 1994;Mu et al., 1995;Colombo et al., 1997;Ridley, 2001;Burgoyne and Clague, 2003;Lawe et al., 2003;Donaldson, 2005).The actin cytosk...

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Cortactin is necessary for E-cadherin–mediated contact formation and actin reorganization

Cited by 162 publications

References 38 publications

EMT, the cytoskeleton, and cancer cell invasion

EMT, the cytoskeleton, and cancer cell invasion

Making and breaking contacts: the cellular biology of cadherin regulation

Protein Kinase Cδ and Calmodulin Regulate Epidermal Growth Factor Receptor Recycling from Early Endosomes through Arp2/3 Complex and Cortactin

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