Scribble, Erbin, and Lano redundantly regulate epithelial polarity and apical adhesion complex

The basolateral protein Scribble (Scrib), a member of the LAP protein family, is essential for epithelial apicobasal polarity (ABP) in Drosophila. However, a conserved function for this protein in mammals is unclear. Here we show that the crucial role for Scrib in ABP has remained obscure due to the compensatory function of two other LAP proteins, Erbin and Lano. A combined Scrib/Erbin/Lano knockout disorganizes the cell–cell junctions and the cytoskeleton. It also results in mislocalization of several apical (Par6, aPKC, and Pals1) and basolateral (Llgl1 and Llgl2) identity proteins. These defects can be rescued by the conserved “LU” region of these LAP proteins. Structure–function analysis of this region determined that the so-called LAPSDb domain is essential for basolateral targeting of these proteins, while the LAPSDa domain is essential for supporting the membrane basolateral identity and binding to Llgl. In contrast to the key role in Drosophila, mislocalization of Llgl proteins does not appear to be critical in the scrib ABP phenotype.

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Desmoplakin Is Required Early in Development for Assembly of Desmosomes and Cytoskeletal Linkage

The Journal of Cell Biology ◽

10.1083/jcb.143.7.2009 ◽

1998 ◽

Vol 143 (7) ◽

pp. 2009-2022 ◽

Cited By ~ 214

Author(s):

G. Ian Gallicano ◽

Panos Kouklis ◽

Christoph Bauer ◽

Mei Yin ◽

Valeri Vasioukhin ◽

...

Keyword(s):

Critical Role ◽

Early Embryo ◽

Cell Junctions ◽

Epithelial Polarity ◽

Tissue Architecture ◽

Desmosomal Cadherins ◽

Tissue Integrity ◽

Classical Cadherins ◽

Mediate Cell ◽

Cell Cell

Desmosomes first assemble in the E3.5 mouse trophectoderm, concomitant with establishment of epithelial polarity and appearance of a blastocoel cavity. Throughout development, they increase in size and number and are especially abundant in epidermis and heart muscle. Desmosomes mediate cell–cell adhesion through desmosomal cadherins, which differ from classical cadherins in their attachments to intermediate filaments (IFs), rather than actin filaments. Of the proteins implicated in making this IF connection, only desmoplakin (DP) is both exclusive to and ubiquitous among desmosomes. To explore its function and importance to tissue integrity, we ablated the desmoplakin gene. Homozygous −/− mutant embryos proceeded through implantation, but did not survive beyond E6.5. Mutant embryos proceeded through implantation, but did not survive beyond E6.5. Surprisingly, analysis of these embryos revealed a critical role for desmoplakin not only in anchoring IFs to desmosomes, but also in desmosome assembly and/or stabilization. This finding not only unveiled a new function for desmoplakin, but also provided the first opportunity to explore desmosome function during embryogenesis. While a blastocoel cavity formed and epithelial cell polarity was at least partially established in the DP (−/−) embryos, the paucity of desmosomal cell–cell junctions severely affected the modeling of tissue architecture and shaping of the early embryo.

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A model system for cell adhesion and signal transduction in Drosophila

Development ◽

10.1242/dev.119.supplement.163 ◽

1993 ◽

Vol 119 (Supplement) ◽

pp. 163-176 ◽

Cited By ~ 5

Author(s):

Mark Peifer ◽

Sandra Orsulic ◽

Li-Mei Pai ◽

Joseph Loureiro

Keyword(s):

Cell Adhesion ◽

Function Analysis ◽

Cell Communication ◽

Adherens Junction ◽

Cell Junctions ◽

Direct Role ◽

Junction Protein ◽

Wingless Signaling ◽

Segment Polarity ◽

Cell Cell

Cells must cooperate and communicate to form a multicellular animal. Information about the molecules required for these processes have come from a variety of sources; the convergence between the studies of particular molecules by vertebrate cell biologists and the genes identified by scientists investigating development in Drosophila has been especially fruitful. We are interested in the connection between cadherin proteins that regulate cell-cell adhesion and the wingless/wnt-1 cell-cell signaling molecules controlling pattern formation during development. The Drosophila segment polarity gene armadillo, homolog of the vertebrate adherens junction protein-catenin, is required for both cell adhesion and wg signaling. We review what is known about wingless signaling in Drosophila, and discuss the role of cell-cell junctions in both cell adhesion and cell communication. We then describe the results of our preliminary structure-function analysis of Armadillo protein in both cell adhesion and wingless signaling. Finally, we discuss evidence supporting a direct role for Armadillo and adherens junction in transduction of wingless signal.

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Basolateral localization of MMP14 drives apicobasal polarity change during EMT independently of its catalytic activity

10.1101/402180 ◽

2018 ◽

Author(s):

Cyril Andrieu ◽

Audrey Montigny ◽

Dominique Alfandari ◽

Eric Theveneau

Keyword(s):

Extracellular Matrix ◽

Catalytic Activity ◽

Epithelial Mesenchymal Transition ◽

Cell Junctions ◽

Loss Of Function ◽

Mesenchymal Transition ◽

Apicobasal Polarity ◽

Promote Cell Migration ◽

Polarity Change ◽

Cell Cell

SummaryThe transmembrane Matrix Metalloproteinase MMP14/MT1-MMP is known to promote cell migration by cleavage of the extracellular matrix. To initiate migration, epithelial cells need to gain mesenchymal attributes. They reduce cell-cell junctions and apicobasal polarity and gain migratory capabilities. This process is named epithelial-mesenchymal transition (EMT). MMP14’s implication in EMT is still ill-defined. We used chick neural crest (NC) cells as a model to explore the function of MMP14 in physiological EMT. Our results show that MMP14 is expressed by chick NC cells. However, it is its subcellular localization, rather than its expression, that correlates with EMT. MMP14 is first apical and switches to basolateral domains during EMT. Loss of function and rescue experiments show that MMP14 is involved in EMT independently of its catalytic activity. It lies downstream of pro-EMT genes and upstream of cell polarity. We found that basolateral localization of MMP14 is required and sufficient to induce polarity change in NC cells and neuroepithelial cells, respectively. These effects on polarity occur without impact on cell-cell adhesion or the extracellular matrix. Overall, our data points to a new function of MMP14 in EMT that will need to be further explored in other systems such as cancer cells.

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Recycling of E-Cadherin

The Journal of Cell Biology ◽

10.1083/jcb.146.1.219 ◽

1999 ◽

Vol 146 (1) ◽

pp. 219-232 ◽

Cited By ~ 225

Author(s):

Tam Luan Le ◽

Alpha S. Yap ◽

Jennifer L. Stow

Keyword(s):

Cell Surface ◽

Cell Junctions ◽

Cell Contact ◽

Epithelial Polarity ◽

Cell Contacts ◽

Epithelial Development ◽

The Reformation ◽

Intracellular Compartments ◽

E Cadherin ◽

Cell Cell

E-Cadherin plays critical roles in many aspects of cell adhesion, epithelial development, and the establishment and maintenance of epithelial polarity. The fate of E-cadherin once it is delivered to the basolateral cell surface, and the mechanisms which govern its participation in adherens junctions, are not well understood. Using surface biotinylation and recycling assays, we observed that some of the cell surface E-cadherin is actively internalized and is then recycled back to the plasma membrane. The pool of E-cadherin undergoing endocytosis and recycling was markedly increased in cells without stable cell-cell contacts, i.e., in preconfluent cells and after cell contacts were disrupted by depletion of extracellular Ca2+, suggesting that endocytic trafficking of E-cadherin is regulated by cell-cell contact. The reformation of cell junctions after replacement of Ca2+ was then found to be inhibited when recycling of endocytosed E-cadherin was disrupted by bafilomycin treatment. The endocytosis and recycling of E-cadherin and of the transferrin receptor were similarly inhibited by potassium depletion and by bafilomycin treatment, and both proteins were accumulated in intracellular compartments by an 18°C temperature block, suggesting that endocytosis may occur via a clathrin-mediated pathway. We conclude that a pool of surface E-cadherin is constantly trafficked through an endocytic, recycling pathway and that this may provide a mechanism for regulating the availability of E-cadherin for junction formation in development, tissue remodeling, and tumorigenesis.

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The F-BAR domain of SRGP-1 facilitates cell–cell adhesion during C. elegans morphogenesis

The Journal of Cell Biology ◽

10.1083/jcb.201005082 ◽

2010 ◽

Vol 191 (4) ◽

pp. 761-769 ◽

Cited By ~ 44

Author(s):

Ronen Zaidel-Bar ◽

Michael J. Joyce ◽

Allison M. Lynch ◽

Kristen Witte ◽

Anjon Audhya ◽

...

Keyword(s):

Cell Adhesion ◽

Molecular Mechanisms ◽

Function Analysis ◽

Membrane Dynamics ◽

Protein Domain ◽

Cell Junctions ◽

Cell Junction ◽

Loss Of Function ◽

Bar Domain ◽

Cell Cell

Robust cell–cell adhesion is critical for tissue integrity and morphogenesis, yet little is known about the molecular mechanisms controlling cell–cell junction architecture and strength. We discovered that SRGP-1 is a novel component of cell–cell junctions in Caenorhabditis elegans, localizing via its F-BAR (Bin1, Amphiphysin, and RVS167) domain and a flanking 200–amino acid sequence. SRGP-1 activity promotes an increase in membrane dynamics at nascent cell–cell contacts and the rapid formation of new junctions; in addition, srgp-1 loss of function is lethal in embryos with compromised cadherin–catenin complexes. Conversely, excess SRGP-1 activity leads to outward bending and projections of junctions. The C-terminal half of SRGP-1 interacts with the N-terminal F-BAR domain and negatively regulates its activity. Significantly, in vivo structure–function analysis establishes a role for the F-BAR domain in promoting rapid and robust cell adhesion during embryonic closure events, independent of the Rho guanosine triphosphatase–activating protein domain. These studies establish a new role for this conserved protein family in modulating cell–cell adhesion.

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