Requirements for adherens junction components in the interaction between epithelial tissues during dorsal closure in Drosophila

Abstract Rap1 belongs to the highly conserved Ras subfamily of small GTPases. In Drosophila, Rap1 plays a critical role in many different morphogenetic processes, but the molecular mechanisms executing its function are unknown. Here, we demonstrate that Canoe (Cno), the Drosophila homolog of mammalian junctional protein AF-6, acts as an effector of Rap1 in vivo. Cno binds to the activated form of Rap1 in a yeast two-hybrid assay, the two molecules colocalize to the adherens junction, and they display very similar phenotypes in embryonic dorsal closure (DC), a process that relies on the elongation and migration of epithelial cell sheets. Genetic interaction experiments show that Rap1 and Cno act in the same molecular pathway during DC and that the function of both molecules in DC depends on their ability to interact. We further show that Rap1 acts upstream of Cno, but that Rap1, unlike Cno, is not involved in the stimulation of JNK pathway activity, indicating that Cno has both a Rap1-dependent and a Rap1-independent function in the DC process.

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The Genes raw and ribbon Are Required for Proper Shape of Tubular Epithelial Tissues in Drosophila

Genetics ◽

10.1093/genetics/147.1.243 ◽

1997 ◽

Vol 147 (1) ◽

pp. 243-253 ◽

Cited By ~ 1

Author(s):

Joseph Jack ◽

Guy Myette

Keyword(s):

Embryonic Development ◽

Salivary Glands ◽

Cell Shape ◽

Malpighian Tubules ◽

Dorsal Closure ◽

Epithelial Tissues ◽

Cell Rearrangement

Abstract The products of two genes, raw and ribbon (rib), are required for the proper morphogenesis of a variety of tissues. Malpighian tubules mutant for raw or rib are wider and shorter than normal tubules, which are only two cells in circumference when they are fully formed. The mutations alter the shape of the tubules beginning early in their formation and block cell rearrangement late in development, which normally lengthens and narrows the tubes. Mutations of both genes affect a number of other tissues as well. Both genes are required for dorsal closure and retraction of the CNS during embryonic development. In addition, rib mutations block head involution, and broaden and shorten other tubular epithelia (salivary glands, tracheae, and hindgut) in much same manner as they alter the shape of the Malpighian tubules. In tissues in which the shape of cells can be observed readily, rib mutations alter cell shape, which probably causes the change in shape of the organs that are affected. In double mutants raw enhances the phenotypes of all the tissues that are affected by rib but unaffected by raw alone, indicating that raw is also active in these tissues.

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The Drosophila Afadin and ZO-1 homologs Canoe and Polychaetoid act in parallel to maintain epithelial integrity when challenged by adherens junction remodeling

10.1101/609123 ◽

2019 ◽

Author(s):

Lathiena A. Manning ◽

Kia Z. Perez-Vale ◽

Kristina N. Schaefer ◽

Mycah T. Sewell ◽

Mark Peifer

Keyword(s):

Cultured Cells ◽

Adherens Junction ◽

Leading Edge ◽

Cell Junctions ◽

Dorsal Closure ◽

Epithelial Integrity ◽

Tissue Integrity ◽

Cell Intercalation ◽

Actomyosin Cytoskeleton ◽

Cell Cell

AbstractDuring morphogenesis cells must change shape and move without disrupting tissue integrity. This requires cell-cell junctions to allow dynamic remodeling while resisting force generated by the actomyosin cytoskeleton. Multiple proteins play roles in junctional-cytoskeletal linkage, but the mechanisms by which they act remain unclear. Drosophila Canoe maintains adherens junction-cytoskeletal linkage during gastrulation. Canoe’s mammalian homolog Afadin plays similar roles in cultured cells, working in parallel with ZO-1 proteins, particularly at multicellular junctions. We took these insights back into the fly embryo, exploring how cells maintain epithelial integrity when challenged by adherens junction remodeling during germband extension and dorsal closure. We found Canoe helps cells maintain junctional-cytoskeletal linkage when challenged by the junctional remodeling inherent in mitosis, cell intercalation and neuroblast invagination, or by forces generated by the actomyosin cable at the leading edge. However, even in the absence of Canoe many cells retain epithelial integrity. This is explained by a parallel role played by the ZO-1 homolog Polychaetoid. In embryos lacking both Canoe and Polychaetoid, cell junctions fail early, with multicellular junctions especially sensitive, leading to widespread loss of epithelial integrity. Our data suggest Canoe and Polychaetoid stabilize Bazooka/Par3 at cell-cell junctions, helping maintain balanced apical contractility and tissue integrity.

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Expression von Tight- und Adherens-Junction Proteinen im Colitis ulcerosa assoziierten Kolonkarzinom: Hochregulierung von Claudin-1, -3, -4 und β-Catenin

Zeitschrift für Gastroenterologie ◽

10.1055/s-2007-988412 ◽

2007 ◽

Vol 45 (08) ◽

Author(s):

ST Mees ◽

R Mennigen ◽

M Utech ◽

N Senninger ◽

M Brüwer

Keyword(s):

Colitis Ulcerosa ◽

Adherens Junction

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Mislocalization of Adherens Junction- Associated Proteins in a Patient with Darier Disease

SKIN The Journal of Cutaneous Medicine ◽

10.25251/skin.2.3.9 ◽

2018 ◽

Vol 2 (3) ◽

pp. 184-201

Author(s):

George D Glinos ◽

Irena Pastar ◽

Marjana Tomic-Canic ◽

Rivka C Stone

Keyword(s):

Adherens Junction ◽

Cellular Adhesion ◽

Calcium Flux ◽

Keratinocyte Differentiation ◽

Calcium Dependent ◽

Endoplasmic Reticulum Calcium ◽

Darier Disease ◽

Associated Proteins ◽

Attachment Proteins ◽

E Cadherin

Darier disease (DD) is an autosomal dominant keratinizing genodermatosis that manifests clinically with red-brown pruritic papules in a seborrheic distribution often in association with palmoplantar pits and dystrophic nail changes. It is caused by mutation in ATP2A2 which encodes a sarco/endoplasmic reticulum calcium ATPase isoform 2 (SERCA2) pump that regulates calcium flux. Consequent alteration of intracellular calcium homeostasis is thought to impair trafficking of cellular adhesion proteins and to lead to aberrant keratinocyte differentiation, contributing to the characteristic histopathologic features of acantholysis and dyskeratosis in DD, though the precise mechanisms are incompletely understood. Previous studies have identified defective localization of desmosomal attachment proteins in skin biopsies and cultured keratinocytes from DD patients, but reports of effects on adherens junction proteins (including calcium-dependent E-cadherin) are conflicting. Here we describe a case of DD presenting with characteristic clinical and histologic features in which we performed immunofluorescence staining of four adherens junction-associated proteins (E-cadherin, α-catenin, β-catenin, and vinculin). In lesional (acantholytic) DD skin, we identified loss of distinctive bright membranous staining that was present at the periphery of keratinocytes throughout the epidermis in the healthy skin of a matched donor. Perilesional (non-acantholytic) portions of DD skin partially recapitulated the normal phenotype. Our findings support a role for SERCA2 dysfunction in impaired assembly of adherens junctions, which together with defective desmosomes contribute to acantholysis in DD.

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