Hemicentin, a conserved extracellular member of the immunoglobulin superfamily, organizes epithelial and other cell attachments into oriented line-shaped junctions

him-4 mutations cause a novel syndrome of tissue fragility, defective cell migration and chromosome instability in Caenorhabditis elegans. Null mutants have abnormal escape reflex, mispositioning of the vas deferens and uterus, and mitotic chromosome loss and multinucleate cells in the germline. The him-4 gene product, hemicentin, is a conserved extracellular matrix protein with 48 tandem immunoglobulin repeats flanked by novel terminal domains. Secreted from skeletal muscle and gonadal leader cells, hemicentin assembles into fine tracks at specific sites, where it contracts broad regions of cell contact into oriented linear junctions. Some tracks organize hemidesmosomes in the overlying epidermis. Hemicentin tracks facilitate mechanosensory neuron anchorage to the epidermis, gliding of the developing gonad along epithelial basement membranes and germline cellularization.

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Venular basement membranes contain specific matrix protein low expression regions that act as exit points for emigrating neutrophils

Journal of Experimental Medicine ◽

10.1084/jem.20051210 ◽

2006 ◽

Vol 203 (6) ◽

pp. 1519-1532 ◽

Cited By ~ 236

Author(s):

Shijun Wang ◽

Mathieu-Benoit Voisin ◽

Karen Y. Larbi ◽

John Dangerfield ◽

Christoph Scheiermann ◽

...

Keyword(s):

Extracellular Matrix ◽

Serine Proteases ◽

Matrix Protein ◽

Unit Area ◽

Protein Localization ◽

Basement Membranes ◽

Extracellular Matrix Protein ◽

Plausible Mechanism ◽

Low Expression

The mechanism of leukocyte migration through venular walls in vivo is largely unknown. By using immunofluorescence staining and confocal microscopy, the present study demonstrates the existence of regions within the walls of unstimulated murine cremasteric venules where expression of key vascular basement membrane (BM) constituents, laminin 10, collagen IV, and nidogen-2 (but not perlecan) are considerably lower (<60%) than the average expression detected in the same vessel. These sites were closely associated with gaps between pericytes and were preferentially used by migrating neutrophils during their passage through cytokine-stimulated venules. Although neutrophil transmigration did not alter the number/unit area of extracellular matrix protein low expression sites, the size of these regions was enlarged and their protein content was reduced in interleukin-1β–stimulated venules. These effects were entirely dependent on the presence of neutrophils and appeared to involve neutrophil-derived serine proteases. Furthermore, evidence was obtained indicating that transmigrating neutrophils carry laminins on their cell surface in vivo. Collectively, through identification of regions of low extracellular matrix protein localization that define the preferred route for transmigrating neutrophils, we have identified a plausible mechanism by which neutrophils penetrate the vascular BM without causing a gross disruption to its intricate structure.

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The extracellular matrix protein WARP is a novel component of a distinct subset of basement membranes

Matrix Biology ◽

10.1016/j.matbio.2008.01.005 ◽

2008 ◽

Vol 27 (4) ◽

pp. 295-305 ◽

Cited By ~ 10

Author(s):

J ALLEN ◽

B BRACHVOGEL ◽

P FARLIE ◽

J FITZGERALD ◽

J BATEMAN

Keyword(s):

Extracellular Matrix ◽

Matrix Protein ◽

Basement Membranes ◽

Extracellular Matrix Protein ◽

Distinct Subset

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Structure and expression of fibulin-2, a novel extracellular matrix protein with multiple EGF-like repeats and consensus motifs for calcium binding.

The Journal of Cell Biology ◽

10.1083/jcb.123.5.1269 ◽

1993 ◽

Vol 123 (5) ◽

pp. 1269-1277 ◽

Cited By ~ 120

Author(s):

T C Pan ◽

T Sasaki ◽

R Z Zhang ◽

R Fässler ◽

R Timpl ◽

...

Keyword(s):

Calcium Binding ◽

Matrix Protein ◽

Mouse Fibroblast ◽

Basement Membranes ◽

Terminal Region ◽

Extracellular Matrix Protein ◽

Cdna Clones ◽

Globular Domain ◽

Northern Blots ◽

Mouse Tissues

A new protein, fibulin-2, was predicted from sequence analysis of cDNA clones obtained from a mouse fibroblast library. This protein consists of a 1195-residue polypeptide preceded by a 26-residue signal peptide. The COOH-terminal region of 787 amino acids contained three anaphylatoxin-related segments (domain I), 11 EGF-like repeats (domain II), 10 of which had a consensus motif for calcium-binding, and a 115-residue globular domain III. Except for two additional EGF-like repeats, this COOH-terminal region showed 43% sequence identity with the previously described fibulin-1 (BM-90). The NH2-terminal 408 residues, unique to fibulin-2, showed no sequence homology to other known proteins and presumably form two additional domains that differ in their cysteine content. Recombinant fibulin-2 was produced and secreted by human cell clones as a disulfide-bonded trimer. Rotary shadowing visualized the protein as three 40-45 nm long rods which are connected at one end in a globe-like structure. No significant immunological cross-reaction could be detected between fibulin-1 and fibulin-2. Production of the fibulin-2 was demonstrated by Northern blots and radioimmunoassay in fibroblasts but not in several tumor cell lines. Together with the observation that the serum level of fibulin-2 is 1,000-fold lower than that of fibulin-1, the data indicate that these two isoforms are not always coordinately expressed. This is also suggested by Northern blots of tissue mRNAs and by immunofluorescence localizations using mouse tissues. The latter studies also demonstrated an extracellular localization for fibulin-2 in basement membranes and other connective tissue compartments.

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Lutheran blood group glycoprotein and its newly characterized mouse homologue specifically bind α5 chain-containing human laminin with high affinity

Blood ◽

10.1182/blood.v97.1.312 ◽

2001 ◽

Vol 97 (1) ◽

pp. 312-320 ◽

Cited By ~ 90

Author(s):

Stephen F. Parsons ◽

Gloria Lee ◽

Frances A. Spring ◽

Thiebaut-Noel Willig ◽

Luanne L. Peters ◽

...

Keyword(s):

Sickle Cell Disease ◽

Blood Group ◽

Sickle Cell ◽

Matrix Protein ◽

Extracellular Matrix Protein ◽

Immunoglobulin Superfamily ◽

Cell Disease ◽

Amino Acid Sequence Level ◽

High Affinity ◽

Mouse Homologue

Abstract Lutheran blood group glycoproteins (Lu gps) are receptors for the extracellular matrix protein, laminin. Studies suggest that Lu gps may contribute to vaso-occlusion in sickle cell disease and it has recently been shown that sickle cells adhere to laminin isoforms containing the α5 chain (laminin 10/11). Laminin α5 is present in the subendothelium and is also a constituent of bone marrow sinusoids, suggesting a role for the Lu/laminin interaction in erythropoiesis. The objectives of the current study were to define more precisely the molecular interactions of the extracellular and intracellular regions of human Lu and to clone and characterize a mouse homologue. To this end, complementary DNA and genomic clones for the mouse homologue were sequenced and the mouse Lu gene mapped to a region on chromosome 7 with conserved synteny with human 19q13.2. Mouse and human Lu gps are highly conserved (72% identity) at the amino acid sequence level and both mouse and human Lu gps specifically bind laminin 10/11 with high affinity. Furthermore, the first 3, N-terminal, immunoglobulin superfamily domains of human Lu are critical for this interaction. The results indicated that the cytoplasmic domain of BRIC 221-labeled human Lu gp is linked with the spectrin-based skeleton, affording the speculation that this interaction may be critical for signal transduction. These results further support a role for Lu gps in sickle cell disease and indicate the utility of mouse models to explore the function of Lu gp-laminin 10/11 interaction in normal erythropoiesis and in sickle cell disease.

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Fatty Acids, CD36, Thrombospondin-1, and CD47 in Glioblastoma: Together and/or Separately?

International Journal of Molecular Sciences ◽

10.3390/ijms23020604 ◽

2022 ◽

Vol 23 (2) ◽

pp. 604

Author(s):

Cristiana Tanase ◽

Ana Maria Enciu ◽

Elena Codrici ◽

Ionela Daniela Popescu ◽

Maria Dudau ◽

...

Keyword(s):

Fatty Acids ◽

Matrix Protein ◽

Cumulative Effect ◽

Membrane Receptors ◽

Extracellular Matrix Protein ◽

Immunoglobulin Superfamily ◽

Intratumor Heterogeneity ◽

Brain Lipids ◽

Wide Range ◽

Thrombospondin 1

Glioblastoma (GBM) is one of the most aggressive tumors of the central nervous system, characterized by a wide range of inter- and intratumor heterogeneity. Accumulation of fatty acids (FA) metabolites was associated with a low survival rate in high-grade glioma patients. The diversity of brain lipids, especially polyunsaturated fatty acids (PUFAs), is greater than in all other organs and several classes of proteins, such as FA transport proteins (FATPs), and FA translocases are considered principal candidates for PUFAs transport through BBB and delivery of PUFAs to brain cells. Among these, the CD36 FA translocase promotes long-chain FA uptake as well as oxidated lipoproteins. Moreover, CD36 binds and recognizes thrombospondin-1 (TSP-1), an extracellular matrix protein that was shown to play a multifaceted role in cancer as part of the tumor microenvironment. Effects on tumor cells are mediated by TSP-1 through the interaction with CD36 as well as CD47, a member of the immunoglobulin superfamily. TSP-1/CD47 interactions have an important role in the modulation of glioma cell invasion and angiogenesis in GBM. Separately, FA, the two membrane receptors CD36, CD47, and their joint ligand TSP-1 all play a part in GBM pathogenesis. The last research has put in light their interconnection/interrelationship in order to exert a cumulative effect in the modulation of the GBM molecular network.

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In Vivo and In VitroExpression of Tenascin by Human Thymic Microenvironmental Cells

Developmental Immunology ◽

10.1155/1995/64871 ◽

1995 ◽

Vol 4 (2) ◽

pp. 139-147 ◽

Cited By ~ 8

Author(s):

Claudia Sondermann Freitas ◽

Jurandy Susana Patricia O'Campo Lyra ◽

Sergio Ranto Dalmau ◽

Wilson Savino

Keyword(s):

Extracellular Matrix ◽

Matrix Protein ◽

Basement Membranes ◽

Extracellular Matrix Protein ◽

Thymic Epithelial Cell ◽

Normal Infant ◽

Cell Network ◽

Extracellular Matrix Components

Increasing evidence reveals that extracellular matrix components can be regarded as a group of mediators in intrathymic T-cell migration and/or differentiation. Yet, little is kown about the expression and putative function of one particular extracellular matrix protein, namely, tenascin in the thymus. Herein we investigated, by means of immunocytochemistry, tenascin expression in normal infant and fetal human thymuses, as well as in cultures of thymic microenvironmental cells.In situ, tenascin distribution is restricted to the medulla and cortico-medullary regions of normal thymuses. This pattern thus differed from that of fibronectin, laminin and type IV collagen, in which subseptal basement membranes were strongly labeled. Interestingly, tenascin did not co-localize with the cytokeratin-defined thymic epithelial cell network. This was in keeping with thein vitrodata showing that tenascin-bearing cells were nonepithelial (and probably nonfibroblastic) microenvironmental elements.Studies with fetal thymuses revealed a developmentally regulated expression of tenascin, with a faint but consistent network labeling, in thymic rudiments as early as 12 weeks of gestational age, that progressed to a strong TN expression at 18 weeks of fetal development, which was similar to the distribution pattern observed thereafter, including postnatally.Our results clearly indicated that tenascin is constitutively expressed in the human thymus, since early stages of thymic ontogeny, and suggest that the cell type responsible for its secretion is a nonepithelial microenvironmental cell.

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Distribution of Dystroglycan in Normal Adult Mouse Tissues

Journal of Histochemistry & Cytochemistry ◽

10.1177/002215549804600404 ◽

1998 ◽

Vol 46 (4) ◽

pp. 449-457 ◽

Cited By ~ 124

Author(s):

Madeleine Durbeej ◽

Michael D. Henry ◽

Maria Ferletta ◽

Kevin P. Campbell ◽

Peter Ekblom

Keyword(s):

Epithelial Cells ◽

Matrix Protein ◽

Close Contact ◽

Surface Protein ◽

Basement Membranes ◽

Extracellular Matrix Protein ◽

Adult Mice ◽

Mouse Tissues ◽

Cell Matrix Interactions ◽

Laminin 1

Dystroglycan is a cell surface protein which, in muscle, links the extracellular matrix protein laminin-2 to the intracellular cytoskeleton. Dystroglycan also binds laminin-1 and the binding occurs via the E3 fragment of laminin-1. Recently, it was found that dystroglycan is expressed in developing epithelial cells of the kidney. Moreover, antibodies against dystroglycan can perturb epithelial development in kidney organ culture. Therefore, dystroglycan may be an important receptor for cell–matrix interactions in non-muscle tissues. However, information about the tissue distribution of dystroglycan is limited, especially in adult tissues. Here we show that dystroglycan is present in epithelial cells in several non-muscle organs of adult mice. Dystroglycan is enriched towards the basal side of the epithelial cells that are in close contact with basement membranes. We suggest that dystroglycan is involved in linking basement membranes to epithelial and muscle cells. Dystroglycan may be important for the maintenance of tissue integrity.

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Perinatal Lethality and Endothelial Cell Abnormalities in Several Vessel Compartments of Fibulin-1-Deficient Mice

Molecular and Cellular Biology ◽

10.1128/mcb.21.20.7025-7034.2001 ◽

2001 ◽

Vol 21 (20) ◽

pp. 7025-7034 ◽

Cited By ~ 112

Author(s):

Günter Kostka ◽

Richard Giltay ◽

Wilhelm Bloch ◽

Klaus Addicks ◽

Rupert Timpl ◽

...

Keyword(s):

Extracellular Matrix ◽

Matrix Protein ◽

Early Death ◽

Basement Membranes ◽

Extracellular Matrix Protein ◽

Elastic Fibers ◽

Endothelial Lining ◽

Distinct Component ◽

Lung Inflation ◽

Small Vessels

ABSTRACT The extracellular matrix protein fibulin-1 is a distinct component of vessel walls and can be associated with other ligands present in basement membranes, microfibrils, and elastic fibers. Its biological role was investigated by the targeted inactivation of the fibulin-1 gene in mice. This led to massive hemorrhages in several tissues starting at midgestation, ultimately resulting in the death of almost all homozygous embryos upon birth. Histological analysis demonstrated dilation and ruptures in the endothelial lining of various small vessels but not in that of larger vessels. Kidneys displayed a distinct malformation of glomeruli and disorganization of podocytes. A delayed development of lung alveoli suggested impairment in lung inflation. Immunohistology demonstrated the absence of fibulin-1 in its typical localizations but no aberrant patterns for several other extracellular matrix proteins. Electron microscopy revealed intact basement membranes but very irregular cytoplasmic processes of capillary endothelial cells in the organs that were most severely affected. Absence of fibulin-1 caused considerable blood loss but did not compromise blood clotting. The data indicate a strong but restricted abnormality in some endothelial compartments which, together with some kidney and lung defects, may be responsible for early death.

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