Use of photoactivation and photobleaching to monitor the dynamic regulation of E-cadherin at the plasma membrane

Canel, Marta; Serrels, Alan; Anderson, Kurt I.; Frame, Margaret C.; Brunton, Valerie G.

doi:10.4161/cam.4.4.12661

Cited by 20 publications

(21 citation statements)

References 37 publications

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“…E-cadherin turnover and the relative contributions of lateral diffusion, endocytosis, and recycling have been studied in both tissue culture and in living animals using antibody internalization, biotinylation, FRAP, and photoactivation approaches. These experiments show that E-cadherin exists in at least two pools at the membrane-an immobile fraction that coexists along with a more rapidly diffusing pool (Cavey et al 2008;Canel et al 2010;Bulgakova et al 2013). Mature junctions are enriched in a stable pool of E-cadherin that turns over predominantly through endocytosis and recycling, rather than by dissociation and lateral diffusion (de Beco et al 2009).…”

Section: The Regulation Of Endocytosis In Epithelial Remodelingmentioning

confidence: 87%

Cargo Sorting in the Endocytic Pathway: A Key Regulator of Cell Polarity and Tissue Dynamics

Eaton

Martı́n-Belmonte

2014

Cold Spring Harbor Perspectives in Biology

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The establishment and maintenance of polarized plasma membrane domains is essential for cellular function and proper development of organisms. Epithelial cells polarize along two fundamental axes, the apicobasal and the planar, both depending on finely regulated protein trafficking mechanisms. Newly synthesized proteins destined for either surface domain are processed along the biosynthetic pathway and segregated into distinct subsets of transport carriers emanating from the trans-Golgi network or endosomes. This exocytic trafficking has been identified as essential for proper epithelial polarization. Accumulating evidence now reveals that endocytosis and endocytic recycling play an equally important role in epithelial polarization and the appropriate localization of key polarity proteins. Here, we review recent work in metazoan systems illuminating the connections between endocytosis, postendocytic trafficking, and cell polarity, both apicobasal and planar, in the formation of differentiated epithelial cells, and how these processes regulate tissue dynamics. ENDOCYTOSIS REGULATES APICOBASAL EPITHELIAL POLARITY

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Section: The Regulation Of Endocytosis In Epithelial Remodelingmentioning

confidence: 87%

Cargo Sorting in the Endocytic Pathway: A Key Regulator of Cell Polarity and Tissue Dynamics

Eaton

Martı́n-Belmonte

2014

Cold Spring Harbor Perspectives in Biology

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“…evidence suggests that the mechanism driving this phenomenon is cadherin endocytosis (16,20), no specific flow of cadherincontaining endocytic vesicles from AJs was detected in live imaging experiments (21). Another set of FRAP data, by contrast, showed that up to 50% of cadherin in AJs is immobile during a 5-min period (22)(23)(24)(25)(26). It was suggested therefore that AJs consist of a stable adhesive core and a replaceable periphery (23,26).…”

Section: Significancementioning

confidence: 99%

Spatial and temporal organization of cadherin in punctate adherens junctions

Indra

Choi

Chen

et al. 2018

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

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Adherens junctions (AJs) play a fundamental role in tissue integrity; however, the organization and dynamics of the key AJ transmembrane protein, E-cadherin, both inside and outside of AJs, remain controversial. Here we have studied the distribution and motility of E-cadherin in punctate AJs (pAJs) of A431 cells. Using single-molecule localization microscopy, we show that pAJs in these cells reach more than 1 μm in length and consist of several cadherin clusters with crystal-like density interspersed within sparser cadherin regions. Notably, extrajunctional cadherin appears to be monomeric, and its density is almost four orders of magnitude less than observed in the pAJ regions. Two alternative strategies of tracking cadherin motion within individual junctions show that pAJs undergo actin-dependent rapid-on the order of seconds-internal reorganizations, during which dense clusters disassemble and their cadherins are immediately reused for new clusters. Our results thus modify the classical view of AJs by depicting them as mosaics of cadherin clusters, the short lifetimes of which enable stable overall morphology combined with rapid internal rearrangements.

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“…Furthermore, these clusters do not undergo extensive re-distribution within the membrane owing to constraints imposed by the actin cytoskeleton, suggesting that they represent genuine adhesive structures (Cavey et al, 2008). The use of photobleaching and photoactivation, which allows the tracking of green fluorescent protein (GFP)-E-cadherin within cells, has shown that a fine balance exists between the movement of E-cadherin molecules within, and away from, the cell surface, and that this is important for the modulation of AJs and their adhesive function (Canel et al, 2010a). The dynamics of E-cadherin at AJs is, therefore, of undoubted importance to maintain junction integrity.…”

Section: E-cadherin Membrane Dynamics and Traffickingmentioning

confidence: 99%

E-cadherin–integrin crosstalk in cancer invasion and metastasis

Canel

Serrels

Frame

et al. 2013

Journal of Cell Science

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560

411

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Summary E-cadherin is a single-pass transmembrane protein that mediates homophilic cell-cell interactions. Tumour progression is often associated with the loss of E-cadherin function and the transition to a more motile and invasive phenotype. This requires the coordinated regulation of both E-cadherin-mediated cell-cell adhesions and integrin-mediated adhesions that contact the surrounding extracellular matrix (ECM). Regulation of both types of adhesion is dynamic as cells respond to external cues from the tumour microenvironment that regulate polarity, directional migration and invasion. Here, we review the mechanisms by which tumour cells control the crossregulation between dynamic E-cadherin-mediated cell-cell adhesions and integrin-mediated cell-matrix contacts, which govern the invasive and metastatic potential of tumours. In particular, we will discuss the role of the adhesion-linked kinases Src, focal adhesion kinase (FAK) and integrin-linked kinase (ILK), and the Rho family of GTPases. Key words: E-cadherin, Integrins, Cancer, Invasion Introduction Understanding the processes by which tumour cells invade and metastasise to distant sites (and how to target them), is one of the great challenges in cancer research, as metastatic spread is responsible for ,90% of cancer-related mortality. Tumour cell invasion and metastasis is a complex process that involves multiple steps, including local migration and invasion, dissemination of malignant tumour cells through the lymphatic or haematogenous systems, and the resulting growth or colonization of micrometastatic lesions and their development into macro-metastases. In common with other 'hallmarks' of cancer (Hanahan and Weinberg, 2011), understanding and inhibiting invasion and metastasis are complicated by the multiplicity of underlying mechanisms, the plasticity of cancer cell behaviour and the evolving nature of the microenvironment. One trait that underpins the ability of cancer cells to metastasise is their ability to change the way in which they interact with the surrounding ECM and with adjacent tumour and stromal cells. E-cadherin is a key mediator of cell-cell adhesions in epithelial tissues, and loss of E-cadherin can promote invasive and metastatic behaviour in many epithelial tumours (Birchmeier and Behrens, 1994). However, it is clear that tumour cells can invade with fully intact and functional cell-cell adhesions as collective groups of cells, and that a loosening of cell-cell contacts is sufficient to permit this collective migration and invasion. This requires coordination of cues from the surrounding tumour environment, to regulate both cell-cell and cell-ECM interactions. Here, we review the role of E-cadherin in tumour cell invasion and metastasis, with particular emphasis on the interplay between E-cadherin and cell-ECM interactions that are mediated by integrin matrix receptors. We discuss the key signalling intermediates that regulate this crosstalk, as well as recent work that supports a physical interaction between integrin-and E-cadherin-

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Use of photoactivation and photobleaching to monitor the dynamic regulation of E-cadherin at the plasma membrane

Cited by 20 publications

References 37 publications

Cargo Sorting in the Endocytic Pathway: A Key Regulator of Cell Polarity and Tissue Dynamics

Cargo Sorting in the Endocytic Pathway: A Key Regulator of Cell Polarity and Tissue Dynamics

Spatial and temporal organization of cadherin in punctate adherens junctions

E-cadherin–integrin crosstalk in cancer invasion and metastasis

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