Molecular organisation of cell–matrix contacts: essential multiprotein assemblies in cell and tissue function

2002 ◽  
Vol 4 (1) ◽  
pp. 1-24 ◽  
Author(s):  
Josephine Clare Adams
Keyword(s):  
Extracellular Matrix ◽  
Inflammatory Responses ◽  
Specific Cell ◽  
Functional Categories ◽  
Adhesion Receptors ◽  
Surface Receptors ◽  
Signalling Molecules ◽  
Cell Matrix ◽  
Molecular Organisation ◽  
Specific Cell Surface

The adhesion of cells to their surrounding extracellular matrix has vital roles in embryonic development, inflammatory responses, wound healing and adult tissue homeostasis. Cells attach to extracellular matrix by specific cell-surface receptors, of which the integrins and transmembrane proteoglycans are major representatives. The engagement of adhesion receptors triggers assembly of functional matrix contacts, in which bound matrix components, adhesion receptors and associated intracellular cytoskeletal and signalling molecules form large, localised multiprotein complexes. This review discusses the functional categories of matrix contacts, examples of the biological roles of matrix contacts in normal physiology, and examples of the ways in which abnormalities of matrix contacts are associated with major human diseases.

scholarly journals Developing defined substrates for stem cell culture and differentiation

2018 ◽  
Vol 373 (1750) ◽  
pp. 20170230 ◽  
Author(s):  
Louise Hagbard ◽  
Katherine Cameron ◽  
Paul August ◽  
Christopher Penton ◽  
Malin Parmar ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Stem Cell ◽  
Cell Fate ◽  
Cell Types ◽  
Specific Cell ◽  
Biologically Relevant ◽  
Stem Cell Maintenance ◽  
Signalling Molecules ◽  
Cell Matrix

Over the past few decades, a variety of different reagents for stem cell maintenance and differentiation have been commercialized. These reagents share a common goal in facilitating the manufacture of products suitable for cell therapy while reducing the amount of non-defined components. Lessons from developmental biology have identified signalling molecules that can guide the differentiation process in vitro , but less attention has been paid to the extracellular matrix used. With the introduction of more biologically relevant and defined matrices, that better mimic specific cell niches, researchers now have powerful resources to fine-tune their in vitro differentiation systems, which may allow the manufacture of therapeutically relevant cell types. In this review article, we revisit the basics of the extracellular matrix, and explore the important role of the cell–matrix interaction. We focus on laminin proteins because they help to maintain pluripotency and drive cell fate specification. This article is part of the theme issue ‘Designer human tissue: coming to a lab near you’.

Chondrons from articular cartilage. V. Immunohistochemical evaluation of type VI collagen organisation in isolated chondrons by light, confocal and electron microscopy

1992 ◽  
Vol 103 (4) ◽  
pp. 1101-1110 ◽  
Author(s):  
C.A. Poole ◽  
S. Ayad ◽  
R.T. Gilbert
Keyword(s):  
Electron Microscopy ◽  
Extracellular Matrix ◽  
Articular Cartilage ◽  
Specific Cell ◽  
Potential Contribution ◽  
Collagen Network ◽  
Tail Region ◽  
Type Vi Collagen ◽  
Surface Receptors ◽  
Basal Pole

The pericellular microenvironment around articular cartilage chondrocytes must play a key role in regulating the interaction between the cell and its extracellular matrix. The potential contribution of type VI collagen to this interaction was investigated in this study using isolated canine tibial chondrons embedded in agarose monolayers. The immunohistochemical distribution of an anti-type VI collagen antibody was assessed in these preparations using fluorescence, peroxidase and gold particle probes in combination with light, confocal and transmission electron microscopy. Light and confocal microscopy both showed type VI collagen concentrated in the pericellular capsule and matrix around the chondrocyte with reduced staining in the tail region and the interconnecting segments between adjacent chondrons. Minimal staining was recorded in the territorial and interterritorial matrices. At higher resolution, type VI collagen appeared both as microfibrils and as amorphous deposits that accumulated at the junction of intersecting capsular fibres and microfibrils. Electron microscopy also showed type VI collagen anchored to the chondrocyte membrane at the articular pole of the pericellular capsule and tethered to the radial collagen network through the tail at the basal pole of the capsule. We suggest that type VI collagen plays a dual role in the maintenance of chondron integrity. First, it could bind to the radial collagen network and stabilise the collagens, proteoglycans and glycoproteins of the pericellular microenvironment. Secondly, specific cell surface receptors exist, which could mediate the interaction between the chondrocyte and type VI collagen, providing firm anchorage and signalling potentials between the pericellular matrix and the cell nucleus. In this way type VI collagen could provide a close functional interrelationship between the chondrocyte, its pericellular microenvironment and the load bearing extracellular matrix of adult articular cartilage.

scholarly journals A polymorphic, prespore-specific cell surface glycoprotein is present in the extracellular matrix of Dictyostelium discoideum.

1985 ◽  
Vol 5 (10) ◽  
pp. 2559-2566 ◽  
Author(s):  
W N Grant ◽  
D L Welker ◽  
K L Williams
Keyword(s):  
Extracellular Matrix ◽  
Cell Surface ◽  
Dictyostelium Discoideum ◽  
Genetic Relationships ◽  
Specific Protein ◽  
Surface Glycoprotein ◽  
Specific Cell ◽  
Developmentally Regulated ◽  
Cell Surface Glycoprotein ◽  
Specific Cell Surface

Polymorphisms of a major developmentally regulated prespore-specific protein (PsA) in Dictyostelium discoideum slugs are described. These polymorphisms allowed discrimination between PsA (found on the cell surface and in the extracellular matrix) and a similar extracellular but nonpolymorphic protein, ShA. The two proteins were also distinguished by their differing reactivities with a range of monoclonal antibodies and by their sensitivity to release from the sheath with cellulase. The results are discussed in terms of the molecular and genetic relationships between the cell surface and the extracellular matrix during development.

scholarly journals Studies on the role of specific cell surface receptors in the removal of lipoprotein (a) in man.

1983 ◽  
Vol 71 (5) ◽  
pp. 1431-1441 ◽  
Author(s):  
F Krempler ◽  
G M Kostner ◽  
A Roscher ◽  
F Haslauer ◽  
K Bolzano ◽  
...  
Keyword(s):  
Cell Surface ◽  
Cell Surface Receptors ◽  
Specific Cell ◽  
Lipoprotein A ◽  
Surface Receptors ◽  
Specific Cell Surface

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.

scholarly journals Adeno-Associated Virus Capsids Displaying Immunoglobulin-Binding Domains Permit Antibody-Mediated Vector Retargeting to Specific Cell Surface Receptors

2002 ◽  
Vol 76 (9) ◽  
pp. 4559-4566 ◽  
Author(s):  
Martin U. Ried ◽  
Anne Girod ◽  
Kristin Leike ◽  
Hildegard Büning ◽  
Michael Hallek
Keyword(s):  
Cell Surface ◽  
Binding Domain ◽  
Cell Surface Receptors ◽  
Specific Cell ◽  
Broad Host Range ◽  
Adeno Associated Virus ◽  
Surface Receptors ◽  
Vector Targeting ◽  
Immunoglobulin Binding ◽  
Specific Cell Surface

ABSTRACT Recombinant adeno-associated virus type 2 (rAAV2) is a promising vector for human somatic gene therapy. However, its broad host range is a disadvantage for some applications, because it reduces the specificity of the gene transfer. To overcome this limitation, we sought to create a versatile rAAV vector targeting system which would allow us to redirect rAAV binding to specific cell surface receptors by simple coupling of different ligands to its capsid. For this purpose, an immunoglobulin G (IgG) binding domain of protein A, Z34C, was inserted into the AAV2 capsid at amino acid position 587. The resulting AAV2-Z34C mutants could be packaged and purified to high titers and bound to IgG molecules. rAAV2-Z34C vectors coupled to antibodies against CD29 (β1-integrin), CD117 (c-kit receptor), and CXCR4 specifically transduced distinct human hematopoietic cell lines. In marked contrast, no transduction was seen in the absence of antibodies or in the presence of specific blocking reagents. These results demonstrate for the first time that an immunoglobulin binding domain can be inserted into the AAV2 capsid and coupled to various antibodies, which mediate the retargeting of rAAV vectors to specific cell surface receptors.

A polymorphic, prespore-specific cell surface glycoprotein is present in the extracellular matrix of Dictyostelium discoideum

1985 ◽  
Vol 5 (10) ◽  
pp. 2559-2566
Author(s):  
W N Grant ◽  
D L Welker ◽  
K L Williams
Keyword(s):  
Extracellular Matrix ◽  
Cell Surface ◽  
Dictyostelium Discoideum ◽  
Genetic Relationships ◽  
Specific Protein ◽  
Surface Glycoprotein ◽  
Specific Cell ◽  
Developmentally Regulated ◽  
Cell Surface Glycoprotein ◽  
Specific Cell Surface

Polymorphisms of a major developmentally regulated prespore-specific protein (PsA) in Dictyostelium discoideum slugs are described. These polymorphisms allowed discrimination between PsA (found on the cell surface and in the extracellular matrix) and a similar extracellular but nonpolymorphic protein, ShA. The two proteins were also distinguished by their differing reactivities with a range of monoclonal antibodies and by their sensitivity to release from the sheath with cellulase. The results are discussed in terms of the molecular and genetic relationships between the cell surface and the extracellular matrix during development.

scholarly journals A stoichiometric complex of neurexins and dystroglycan in brain

2001 ◽  
Vol 154 (2) ◽  
pp. 435-446 ◽  
Author(s):  
Shuzo Sugita ◽  
Fumiaki Saito ◽  
Jiong Tang ◽  
Jakob Satz ◽  
Kevin Campbell ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Cell Surface ◽  
Surface Protein ◽  
Surface Proteins ◽  
Sex Hormone Binding Globulin ◽  
Muscular Dystrophies ◽  
Specific Cell ◽  
Mediate Cell Adhesion ◽  
Mediate Cell ◽  
Specific Cell Surface

In nonneuronal cells, the cell surface protein dystroglycan links the intracellular cytoskeleton (via dystrophin or utrophin) to the extracellular matrix (via laminin, agrin, or perlecan). Impairment of this linkage is instrumental in the pathogenesis of muscular dystrophies. In brain, dystroglycan and dystrophin are expressed on neurons and astrocytes, and some muscular dystrophies cause cognitive dysfunction; however, no extracellular binding partner for neuronal dystroglycan is known. Regular components of the extracellular matrix, such as laminin, agrin, and perlecan, are not abundant in brain except in the perivascular space that is contacted by astrocytes but not by neurons, suggesting that other ligands for neuronal dystroglycan must exist. We have now identified α- and β-neurexins, polymorphic neuron-specific cell surface proteins, as neuronal dystroglycan receptors. The extracellular sequences of α- and β-neurexins are largely composed of laminin-neurexin–sex hormone–binding globulin (LNS)/laminin G domains, which are also found in laminin, agrin, and perlecan, that are dystroglycan ligands. Dystroglycan binds specifically to a subset of the LNS domains of neurexins in a tight interaction that requires glycosylation of dystroglycan and is regulated by alternative splicing of neurexins. Neurexins are receptors for the excitatory neurotoxin α-latrotoxin; this toxin competes with dystroglycan for binding, suggesting overlapping binding sites on neurexins for dystroglycan and α-latrotoxin. Our data indicate that dystroglycan is a physiological ligand for neurexins and that neurexins' tightly regulated interaction could mediate cell adhesion between brain cells.

Targeted Therapy for Hematologic Malignancies

2005 ◽  
Vol 12 (2) ◽  
pp. 82-90 ◽  
Author(s):  
Philip Kuriakose
Keyword(s):  
Monoclonal Antibodies ◽  
Targeted Therapy ◽  
Small Molecules ◽  
Targeted Therapies ◽  
Hematologic Malignancies ◽  
Therapeutic Benefit ◽  
Specific Cell ◽  
Surface Receptors ◽  
Toxic Approach ◽  
Specific Cell Surface

Background: The introduction of monoclonal antibodies, either as native molecules or conjugated to radioisotopes or other toxins, has led to new therapeutic options for patients with hematologic malignancies. In addition, the use of small molecules against specific cell surface receptors, enzymes, and proteins has become an important strategy in the treatment of such disorders. Methods: The author reviewed the published clinical trials of monoclonal antibody and other targeted therapies in hematologic malignancies. Results: Results from several trials demonstrate a therapeutic benefit for the use of monoclonal antibodies (either native or conjugated) and other targeted therapies, used alone or in combination with standard cytotoxic chemotherapy. Conclusions: Targeted therapy of hematologic malignancies seems to be an effective and less toxic approach to the treatment of such disorders. Nevertheless, additional studies are needed to determine where and when such management fits into a therapeutic regimen for any given disorder, whether upfront or as salvage therapy, alone or in combination with chemotherapy (concurrent or sequential).

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