scholarly journals Multiple functions for the catenin family member plakoglobin in cadherin-dependent adhesion, fibronectin matrix assembly and Xenopus gastrulation movements

2018 ◽  
Author(s):  
Glen D. Hirsh ◽  
Bette J. Dzamba ◽  
Pooja R. Sonavane ◽  
David R. Shook ◽  
Claire M. Allen ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Actin Binding ◽  
Convergent Extension ◽  
Integrin Receptors ◽  
Matrix Assembly ◽  
Cell Matrix ◽  
Fibronectin Matrix ◽  
Cytoplasmic Tails ◽  
Fibronectin Assembly

AbstractShaping an embryo requires tissue-scale cell rearrangements known as morphogenetic events. These force-dependent processes require cells to adhere to their neighbors, through cadherin-catenin complexes, and to their extracellular matrix substrates, through integrin-based focal contacts. Integrin receptors are not only important for attachment to the extracellular matrix, but also for its fibrillar assembly. Fibrillogenesis requires actomyosin contractility, regulated in part by cadherin-catenin complexes. One such catenin, plakoglobin, mediates the attachment of actin stress fibers to cadherin cytoplasmic tails through its interactions with actin-binding proteins. In Xenopus gastrulae, plakoglobin has been identified as an essential member in the force-induced collective migration of the mesendoderm tissue. In the current study, we have further characterized the role of plakoglobin in two additional morphogenetic processes, epiboly and convergent extension. Plakoglobin-deficient tadpoles are 40% shorter and gastrulae contain notochords that are 60% wider than stage-matched controls, indicating convergent extension defects. The radially intercalating ectoderm of morphant animal caps is nearly twice as thick as controls. Furthermore, morphant embryos exhibit a failure to assemble a fibronectin matrix at the notochord-somite-boundary or along the blastocoel roof. The loss of the fibronectin matrix, while not due to changes in overall patterning, is a result of a failure to assemble the soluble dimers into long fibrils. The force of attachment to a cadherin or fibronectin substrate is reduced in plakoglobin morphants, indicating defects in adhesion to both cadherin and fibronectin. These data suggest that plakoglobin regulates morphogenesis and fibronectin assembly through cell-cell and cell-matrix adhesion.

Molecular regulation of cellular invasion— role of gelatinase A and TIMP-2

1996 ◽  
Vol 74 (6) ◽  
pp. 823-831 ◽  
Author(s):  
Anita E. Yu ◽  
Robert E. Hewitt ◽  
David E. Kleiner ◽  
William G. Stetler-Stevenson
Keyword(s):  
Extracellular Matrix ◽  
Matrix Metalloproteinases ◽  
Tissue Inhibitors Of Metalloproteinases ◽  
Gelatinase A ◽  
Cellular Mechanisms ◽  
Cell Matrix ◽  
Matrix Interactions ◽  
The Matrix ◽  
Cell Matrix Interactions

Extracellular matrix (ECM) turnover is an event that is tightly regulated. Much of the coordinate (physiological) or discoordinate (pathological) degradation of the ECM is catalyzed by a class of proteases known as the matrix metalloproteinases (MMPs) or matrixins. Matrixins are a family of homologous Zn atom dependent endopeptidases that are usually secreted from cells as inactive zymogens. Net degradative activity in the extracellular environment is regulated by specific activators and inhibitors. One member of the matrixin family, gelatinase A, is regulated differently from other MMPs, suggesting that it may play a unique role in cell–matrix interactions, including cell invasion. The conversion from the 72 kDa progelatinase A to the active 62 kDa species may be a key event in the acquisition of invasive potential. This discussion reviews some recent findings on the cellular mechanisms involved in progelatinase A activation and, in particular, the role of tissue inhibitor of matrix metalloproteinases-2 (TIMP-2) and transmembrane containing metalloproteinases (MT-MMP) in this process.Key words: tissue inhibitors of metalloproteinases, metalloproteinase, gelatinases, extracellular matrix, activation.

scholarly journals Extracellular Matrix and Integrins in Embryonic Stem Cell Differentiation

2015 ◽  
Vol 8s2 ◽  
pp. BCI.S30377 ◽  
Author(s):  
Han Wang ◽  
Xie Luo ◽  
Jake Leighton
Keyword(s):  
Extracellular Matrix ◽  
Pancreatic Beta Cells ◽  
Embryonic Stem ◽  
Stem Cell Differentiation ◽  
Embryonic Stem Cell Differentiation ◽  
In Vitro Differentiation ◽  
Integrin Receptors

Embryonic stem cells (ESCs) are pluripotent cells with great therapeutic potentials. The in vitro differentiation of ESC was designed by recapitulating embryogenesis. Significant progress has been made to improve the in vitro differentiation protocols by toning soluble maintenance factors. However, more robust methods for lineage-specific differentiation and maturation are still under development. Considering the complexity of in vivo embryogenesis environment, extracellular matrix (ECM) cues should be considered besides growth factor cues. ECM proteins bind to cells and act as ligands of integrin receptors on cell surfaces. Here, we summarize the role of the ECM and integrins in the formation of three germ layer progenies. Various ECM–integrin interactions were found, facilitating differentiation toward definitive endoderm, hepatocyte-like cells, pancreatic beta cells, early mesodermal progenitors, cardiomyocytes, neuroectoderm lineages, and epidermal cells, such as keratinocytes and melanocytes. In the future, ECM combinations for the optimal ESC differentiation environment will require substantial study.

Regulation of protrusive and contractile cell-matrix contacts

2002 ◽  
Vol 115 (2) ◽  
pp. 257-265
Author(s):  
Josephine Clare Adams
Keyword(s):  
Extracellular Matrix ◽  
Cell Adhesion ◽  
Cell Surface ◽  
Cellular Level ◽  
Functional Categories ◽  
Molecular Processes ◽  
Matrix Assembly ◽  
Diverse Range ◽  
Cell Matrix ◽  
Multicellular Organisms

The extracellular matrix is vital for tissue organisation in multicellular organisms. Cells attach to the extracellular matrix at discrete points on the cell surface, termed cell-matrix contacts. In general molecular terms, these contacts are assembled from large multiprotein complexes. However, many forms of matrix contacts can be distinguished by microscopy or by biochemical criteria, and these fulfil a diverse range of roles associated with cell adhesion, guidance, migration, matrix assembly, differentiation and survival. Two major functional categories are the protrusive and contractile matrix contacts. I describe contexts for the formation of protrusive or contractile contacts and discuss recent information on the molecular processes by which these contacts are specified, coordinated and regulated at a cellular level.

Potential role of RGD-binding integrins in mammalian lung branching morphogenesis

Development ◽  
1991 ◽  
Vol 112 (2) ◽  
pp. 551-558 ◽  
Author(s):  
J. Roman ◽  
C.W. Little ◽  
J.A. McDonald
Keyword(s):  
Lung Development ◽  
Branching Morphogenesis ◽  
Integrin Receptors ◽  
Murine Lung ◽  
Cell Matrix ◽  
Matrix Interactions ◽  
Mammalian Lung ◽  
Cell Matrix Interactions ◽  
Lung Branching

Cell-matrix interactions are generally considered critical for normal lung development. This is particularly likely to be true during the glandular stage, when the primitive airways are formed through a process termed branching morphogenesis. Integrins, transmembrane receptors that bind to extracellular matrices, are likely to mediate important interactions between embryonic cells and their matrices during branching morphogenesis. In this report, we examine the role of integrin receptors in this process. Immunohistochemical studies revealed that the integrins VLA 3, VLA 5 and integrin receptors to vitronectin are expressed in the epithelium and/or mesenchyme during the glandular stage of murine lung development. To correlate expression with function, an in vitro model of murine lung branching morphogenesis was utilized to examine branching in the presence of inhibitors of ligand binding to integrin receptors. One such reagent, a hexapeptide containing the RGD (Arg-Gly-Asp) sequence, diminished branching and resulted in an abnormal morphology, whereas a control peptide RGESP (Arg-Gly-Glu-Ser-Pro) had no effect. These findings suggest a critical role for cell-matrix interactions mediated via integrin receptors in early stages of mammalian lung development.

Role of the carboxyl-terminal Fib2 domain in fibronectin matrix assembly

1995 ◽  
Vol 108 (3) ◽  
pp. 907-915 ◽  
Author(s):  
K. Ichihara-Tanaka ◽  
K. Titani ◽  
K. Sekiguchi
Keyword(s):  
Residual Activity ◽  
Significant Activity ◽  
Matrix Assembly ◽  
En Bloc ◽  
Proteolytic Fragment ◽  
Cultured Fibroblasts ◽  
Fibronectin Matrix ◽  
The Matrix ◽  
Assembly Activity

A truncated form of fibronectin consisting of the N-terminal 70 kDa and C-terminal 37 kDa regions, designated r70F2, retained the ability to assemble into the extracellular matrix when expressed in cultured fibroblasts (Ichihara-Tanaka et al. (1992) FEBS Lett. 299, 155–158). To elucidate the role of the C-terminal 37 kDa region in fibronectin matrix assembly, we expressed a panel of mutant forms of r70F2 with various deletions and amino acid substitutions in mouse L cells. Although substitution of Ser for two Cys residues in the C-terminal dimerforming segment led to a marked reduction in the matrix assembly activity of r70F2, the resulting monomeric r70F2 still retained a low, but significant activity to assemble into the matrix. Neither the N-terminal 70 kDa nor the C-terminal 37 kDa regions, when expressed as monomeric forms, exhibited any residual activity, suggesting that the core domain of the 37 kDa region consisting of III15 and I10 through I12 modules, termed Fib2 domain, is actively involved in the matrix assembly of r70F2. In support of the role of Fib2 domain, the proteolytic fragment derived from the 37 kDa region inhibited the assembly of r70F2. Furthermore, en bloc deletion of the Fib2 domain or deletion of the I10 through I12 modules from r70F2 resulted in a marked decrease of the matrix assembly activity.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Fibronectin Polymerization Regulates the Composition and Stability of Extracellular Matrix Fibrils and Cell-Matrix Adhesions

2002 ◽  
Vol 13 (10) ◽  
pp. 3546-3559 ◽  
Author(s):  
Jane Sottile ◽  
Denise C. Hocking
Keyword(s):  
Extracellular Matrix ◽  
Collagen I ◽  
Matrix Deposition ◽  
Matrix Adhesion ◽  
Cell Matrix ◽  
Adhesion Sites ◽  
Fibronectin Matrix ◽  
Thrombospondin 1 ◽  
Fibronectin Deposition ◽  
Cell Matrix Adhesion

Remodeling of extracellular matrices occurs during development, wound healing, and in a variety of pathological processes including atherosclerosis, ischemic injury, and angiogenesis. Thus, identifying factors that control the balance between matrix deposition and degradation during tissue remodeling is essential for understanding mechanisms that regulate a variety of normal and pathological processes. Using fibronectin-null cells, we found that fibronectin polymerization into the extracellular matrix is required for the deposition of collagen-I and thrombospondin-1 and that the maintenance of extracellular matrix fibronectin fibrils requires the continual polymerization of a fibronectin matrix. Further, integrin ligation alone is not sufficient to maintain extracellular matrix fibronectin in the absence of fibronectin deposition. Our data also demonstrate that the retention of thrombospondin-1 and collagen I into fibrillar structures within the extracellular matrix depends on an intact fibronectin matrix. An intact fibronectin matrix is also critical for maintaining the composition of cell–matrix adhesion sites; in the absence of fibronectin and fibronectin polymerization, neither α5β1 integrin nor tensin localize to fibrillar cell–matrix adhesion sites. These data indicate that fibronectin polymerization is a critical regulator of extracellular matrix organization and stability. The ability of fibronectin polymerization to act as a switch that controls the organization and composition of the extracellular matrix and cell–matrix adhesion sites provides cells with a means of precisely controlling cell-extracellular matrix signaling events that regulate many aspects of cell behavior including cell proliferation, migration, and differentiation.

scholarly journals Essential role of MARCKS in cortical actin dynamics during gastrulation movements

2004 ◽  
Vol 164 (2) ◽  
pp. 169-174 ◽  
Author(s):  
Hidekazu Iioka ◽  
Naoto Ueno ◽  
Noriyuki Kinoshita
Keyword(s):  
Wnt Pathway ◽  
Actin Dynamics ◽  
Actin Binding ◽  
Convergent Extension ◽  
Embryonic Cells ◽  
Cortical Actin ◽  
Morphogenetic Movements ◽  
Kinase Substrate ◽  
Cytoskeletal Regulation

Myristoylated alanine-rich C kinase substrate (MARCKS) is an actin-binding, membrane-associated protein expressed during Xenopus embryogenesis. We analyzed its function in cytoskeletal regulation during gastrulation. Here, we show that blockade of its function impaired morphogenetic movements, including convergent extension. MARCKS was required for control of cell morphology, motility, adhesion, protrusive activity, and cortical actin formation in embryonic cells. We also demonstrate that the noncanonical Wnt pathway promotes the formation of lamellipodia- and filopodia-like protrusions and that MARCKS is necessary for this activity. These findings show that MARCKS regulates the cortical actin formation that is requisite for dynamic morphogenetic movements.

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