scholarly journals The cadherins: cell-cell adhesion molecules controlling animal morphogenesis

Development ◽  
1988 ◽  
Vol 102 (4) ◽  
pp. 639-655 ◽  
Author(s):  
M. Takeichi
Keyword(s):  
Cell Adhesion ◽  
Ectopic Expression ◽  
Amino Acid Sequences ◽  
Single Animal ◽  
Cell Layers ◽  
Dependent Cell ◽  
Cell Collective ◽  
Cell Cell

Cadherins are a family of glycoproteins involved in the Ca2+-dependent cell-cell adhesion mechanism which is detected in most kinds of tissues. Inhibition of the cadherin activity with antibodies induces dissociation of cell layers, indicating a fundamental importance of these molecules in maintaining the multicellular structure. Cadherins are divided into subclasses, including E-, N- and P-cadherins. While all subclasses are similar in molecular weight, Ca2+- and protease-sensitivity, each subclass is characterized by a unique tissue distribution pattern and immunological specificity. Analysis of amino acid sequences deduced from cDNA encoding these molecules showed that they are integral membrane proteins of 723–748 amino acids long and share common sequences; similarity in the sequences between subclasses is in a range of 50–60% when compared within a single animal species. L cells, with very little endogenous cadherin activity, transfected with the cadherin cDNA acquired high cadherin-mediated aggregating activity. Their colony morphology was altered by the ectopic expression of cadherins from the dispersed type to the compact type, providing direct evidence for a key role of cadherins in cell-cell adhesion. It has been suggested that cadherins bind cells by their homophilic interactions at the extracellular domain and are associated with actin bundles at the cytoplasmic domain. It appears that each cadherin subclass has binding specificity and this molecular family is involved in selective cell-cell adhesion. In development, the expression of each cadherin subclass is spatiotemporally regulated and associated with a variety of morphogenetic events; e.g. the termination or initiation of expression of a cadherin subclass in a given cell collective is correlated with its segregation from or connection with other cell collectives. Antibodies to cadherins were shown to perturb the morphogenesis of some embryonic organs in vitro. These observations suggest that cadherins play a crucial role in construction of tissues and the whole animal body.

The disintegrin-like metalloproteinase ADAM10 is involved in constitutive cleavage of CX3CL1 (fractalkine) and regulates CX3CL1-mediated cell-cell adhesion

Blood ◽  
2003 ◽  
Vol 102 (4) ◽  
pp. 1186-1195 ◽  
Author(s):  
Christian Hundhausen ◽  
Dominika Misztela ◽  
Theo A. Berkhout ◽  
Neil Broadway ◽  
Paul Saftig ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Soluble Form ◽  
Adhesive Properties ◽  
Monocytic Cells ◽  
Murine Fibroblasts ◽  
Cell Layers ◽  
Factor Α ◽  
Necrosis Factor ◽  
Cell Cell

Abstract The CX3C chemokine fractalkine (CX3CL1) exists as a membrane-expressed protein promoting cell-cell adhesion and as a soluble molecule inducing chemotaxis. Transmembrane CX3CL1 is converted into its soluble form by defined proteolytic cleavage (shedding), which can be enhanced by stimulation with phorbol-12-myristate-13-acetate (PMA). PMA-induced CX3CL1 shedding has been shown to involve the tumor necrosis factor-α–converting enzyme (TACE), whereas the constitutive cleavage in unstimulated cells remains elusive. Here we demonstrate a role of the closely related disintegrin-like metalloproteinase 10 (ADAM10) in the constitutive CX3CL1 cleavage. The hydroxamate GW280264X, capable of blocking TACE as well as ADAM10, proved to be an effective inhibitor of the constitutive and the PMA-inducible CX3CL1 cleavage in CX3CL1-expressing ECV-304 cells (CX3CL1–ECV-304), whereas GI254023X, preferentially blocking ADAM10 but not TACE, reduced the constitutive cleavage only. Overexpression of ADAM10 in COS-7 cells enhanced constitutive cleavage of CX3CL1 and, more importantly, in murine fibroblasts deficient of ADAM10 constitutive CX3CL1 cleavage was markedly reduced. Thus, ADAM10 contributes to the constitutive shedding of CX3CL1 in unstimulated cells. Addressing the functional role of CX3CL1 shedding for the adhesion of monocytic cells via membrane-expressed CX3CL1, we found that THP-1 cells adhere to CX3CL1–ECV-304 cells but detach in the course of vigorous washing. Inhibition of ADAM10-mediated CX3CL1 shedding not only increased adhesive properties of CX3CL1–ECV-304 cells but also prevented de-adhesion of bound THP-1 cells. Our data demonstrate that ADAM10 is involved in the constitutive cleavage of CX3CL1 and thereby may regulate the recruitment of monocytic cells to CX3CL1-expressing cell layers.

scholarly journals Regulation of cell–cell adhesion by the cadherin–catenin complex

2008 ◽  
Vol 36 (2) ◽  
pp. 149-155 ◽  
Author(s):  
W. James Nelson
Keyword(s):  
Cell Adhesion ◽  
Actin Cytoskeleton ◽  
Rho Gtpases ◽  
De Novo ◽  
Cytoplasmic Proteins ◽  
Cytoskeleton Reorganization ◽  
Dependent Cell ◽  
And Function ◽  
Cell Cell

Ca2+-dependent cell–cell adhesion is regulated by the cadherin family of cell adhesion proteins. Cadherins form trans-interactions on opposing cell surfaces which result in weak cell–cell adhesion. Stronger cell–cell adhesion occurs by clustering of cadherins and through changes in the organization of the actin cytoskeleton. Although cadherins were thought to bind directly to the actin cytoskeleton through cytoplasmic proteins, termed α- and β-catenin, recent studies with purified proteins indicate that the interaction is not direct, and instead an allosteric switch in α-catenin may mediate actin cytoskeleton reorganization. Organization and function of the cadherin–catenin complex are additionally regulated by phosphorylation and endocytosis. Direct studies of cell–cell adhesion has revealed that the cadherin–catenin complex and the underlying actin cytoskeleton undergo a series of reorganizations that are controlled by the Rho GTPases, Rac1 and RhoA, that result in the expansion and completion of cell–cell adhesion. In the present article, in vitro protein assembly studies and live-cell studies of de novo cell–cell adhesion are discussed in the context of how the cadherin–catenin complex and the actin cytoskeleton regulate cell–cell adhesion.

Granular cells are required for encapsulation of foreign targets by insect haemocytes

1996 ◽  
Vol 109 (8) ◽  
pp. 2053-2060 ◽  
Author(s):  
L.L. Pech ◽  
M.R. Strand
Keyword(s):  
Cell Adhesion ◽  
Granular Cell ◽  
Immunocytochemical Staining ◽  
Granular Cells ◽  
Recognition Sequence ◽  
Capsule Formation ◽  
Insect Haemocytes ◽  
Dependent Cell

Haemocytes play an essential role in defending invertebrates against pathogens and parasites that enter their haemocoel. A primary defense response is encapsulation; a process in which haemocytes attach to the foreign organism and kill it. Whether encapsulation requires cooperation between specific subpopulations of haemocytes is unknown. Using purified subpopulations of haemocytes and an in vitro encapsulation assay, we investigated the process of capsule formation in the insect Pseudoplusia includens. Immunocytochemical staining revealed that capsule formation involves a three step process. Encapsulation began when granular cells attached to the foreign target. This was followed by attachment of multiple layers of plasmatocytes. Termination of capsule formation occurred when a subpopulation of granular cells formed a monolayer around the periphery of the capsule. Neither granular cells nor plasmatocytes were capable of forming a capsule independently. However, plasmatocytes encapsulated targets if granular cells were present or if targets were preincubated in medium conditioned by granular cells. The effect of granular cell-conditioned medium could be blocked by the addition of the cell adhesion recognition sequence, RGDS, but not by RGES. These results demonstrate experimentally that granular cells are required for encapsulation of foreign targets by plasmatocytes in vitro, and that the role of granular cells in this process involves an RGD-dependent cell adhesion mechanism.

The role of cadherins and catenins in gliomagenesis

2006 ◽  
Vol 21 (4) ◽  
pp. 1-4 ◽  
Author(s):  
Kaveh Barami ◽  
Laura Lewis-Tuffin ◽  
Panos Z. Anastasiadis
Keyword(s):  
Cell Adhesion ◽  
Normal Tissue ◽  
Cell Of Origin ◽  
Surface Adhesion ◽  
Therapeutic Approaches ◽  
Calcium Dependent ◽  
New Therapeutic Approaches ◽  
Dependent Cell ◽  
Cell Cell

✓Cell–cell adhesion is a crucial process occurring during normal tissue development. Cadherins are calcium-dependent cell-surface adhesion molecules involved in cell–cell adhesion. They reorganize the actin cytoskeleton via interaction with the catenins. Modulation of the cadherin/catenin system plays a role in cell motility. Dysregulation of the cadherin/catenin assembly has been implicated in various cancers. In this review, the authors summarize all studies focusing on the role of cadherins and catenins in glioma formation. With the emergence of recent data regarding gliomas' putative cell of origin, elucidation of the role of cadherins/catenins in gliomagenesis will become important in devising new therapeutic approaches against such deadly cancers.

scholarly journals Arginylation-dependent regulation of a proteolytic product of talin is essential for cell–cell adhesion

2012 ◽  
Vol 197 (6) ◽  
pp. 819-836 ◽  
Author(s):  
Fangliang Zhang ◽  
Sougata Saha ◽  
Anna Kashina
Keyword(s):  
Cell Adhesion ◽  
Cell Attachment ◽  
Adhesion Formation ◽  
Cell Matrix ◽  
Intracellular Regulation ◽  
Dependent Cell ◽  
Cell Matrix Adhesion ◽  
Proteolytic Product ◽  
Cell Cell

Talin is a large scaffolding molecule that plays a major role in integrin-dependent cell–matrix adhesion. A role for talin in cell–cell attachment through cadherin has never been demonstrated, however. Here, we identify a novel calpain-dependent proteolytic cleavage of talin that results in the release of a 70-kD C-terminal fragment, which serves as a substrate of posttranslational arginylation. The intracellular levels of this fragment closely correlated with the formation of cell–cell adhesions, and this fragment localized to cadherin-containing cell–cell contacts. Moreover, reintroduction of this fragment rescued the cell–cell adhesion defects in arginyltransferase (Ate1) knockout cells, which normally have a very low level of this fragment. Arginylation of this fragment further enhanced its ability to rescue cell–cell adhesion formation. In addition, arginylation facilitated its turnover, suggesting a dual role of arginylation in its intracellular regulation. Thus, our work identifies a novel proteolytic product of talin that is regulated by arginylation and a new role of talin in cadherin-dependent cell–cell adhesion.

Ectopic expression of N-cadherin perturbs histogenesis in Xenopus embryos

Development ◽  
1990 ◽  
Vol 110 (1) ◽  
pp. 97-104 ◽  
Author(s):  
T. Fujimori ◽  
S. Miyatani ◽  
M. Takeichi
Keyword(s):  
Ectopic Expression ◽  
Cell Stage ◽  
Xenopus Embryos ◽  
Cell Layers ◽  
Developmental Role ◽  
Embryonic Morphogenesis

Xenopus embryos express N-cadherin in a pattern similar to that observed in other species, and cells expressing Xenopus N-cadherin can bind to cells expressing chicken N-cadherin in vitro. To investigate the developmental role of this molecule, we injected mRNA encoding chicken N-cadherin into one blastomere of 2-cell-stage Xenopus embryos and examined the effect of its expression on their development. The ectopic expression of N-cadherin occurred in various regions of the injected embryos and induced abnormal histogenesis, such as thickening, clumping or fusion of cell layers. These results suggest that the precise quantitative and qualitative regulation of the expression of cadherins is essential to embryonic morphogenesis.

N-cadherin and N-CAM in myoblast fusion: compared localisation and effect of blockade by peptides and antibodies

1992 ◽  
Vol 103 (4) ◽  
pp. 897-906 ◽  
Author(s):  
R.M. Mege ◽  
D. Goudou ◽  
C. Diaz ◽  
M. Nicolet ◽  
L. Garcia ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Adhesion Molecule ◽  
Synthetic Peptide ◽  
Cell Adhesion Molecule ◽  
Myoblast Fusion ◽  
Immunogold Electron Microscopy ◽  
Dependent Cell ◽  
Leg Muscle

The expression and distribution of two cell adhesion molecules, N-cadherin and N-CAM, at the surface of cultured leg muscle cells from 11-day-old chicken embryos were studied and compared. N-cadherin, which was expressed by fusing myoblasts, was down-regulated on old myotubes while N-CAM was still present. Both molecules, as viewed by confocal microscopy, appeared to have coaccumulated at the areas of contact between fusing myoblasts. However, immunogold electron microscopy did not reveal significant colocalization of N-cadherin and N-CAM, and their segregation after antibody-induced patching suggested the absence of direct interactions between N-cadherin and N-CAM. The role of the Ca2+ dependent cell adhesion molecule N-cadherin in myogenesis was investigated. Myoblast fusion was inhibited (1) with a synthetic peptide containing the H-A-V sequence and (2) with a monoclonal anti-N-cadherin antibody, demonstrating that N-cadherin-mediated cell adhesion is required for myoblast fusion. Under the same conditions no effect of anti-N-CAM antibodies was observed. Taken together these observations suggest that N-cadherin, acting independently from N-CAM, is a major cell adhesion molecule involved in embryonic myoblast fusion in vitro.

scholarly journals Mitochondrion-Dependent Cell Death in TDP-43 Proteinopathies

Biomedicines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 376
Author(s):  
Chantal B. Lucini ◽  
Ralf J. Braun
Keyword(s):  
Cell Death ◽  
Oxygen Species ◽  
In Vivo Models ◽  
Dependent Cell ◽  
Cell Death Mechanisms ◽  
Sting Pathway ◽  
Mitochondrial Membrane Permeabilization

In the last decade, pieces of evidence for TDP-43-mediated mitochondrial dysfunction in neurodegenerative diseases have accumulated. In patient samples, in vitro and in vivo models have shown mitochondrial accumulation of TDP-43, concomitantly with hallmarks of mitochondrial destabilization, such as increased production of reactive oxygen species (ROS), reduced level of oxidative phosphorylation (OXPHOS), and mitochondrial membrane permeabilization. Incidences of TDP-43-dependent cell death, which depends on mitochondrial DNA (mtDNA) content, is increased upon ageing. However, the molecular pathways behind mitochondrion-dependent cell death in TDP-43 proteinopathies remained unclear. In this review, we discuss the role of TDP-43 in mitochondria, as well as in mitochondrion-dependent cell death. This review includes the recent discovery of the TDP-43-dependent activation of the innate immunity cyclic GMP-AMP synthase/stimulator of interferon genes (cGAS/STING) pathway. Unravelling cell death mechanisms upon TDP-43 accumulation in mitochondria may open up new opportunities in TDP-43 proteinopathy research.

Sign in / Sign up

Export Citation Format

Share Document