Drosophila ribosomal protein S19 cDNA sequence.
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Amino Acid Sequence↗
Biomedical subjects
R Chiquet-Ehrismann
Publications and source records attributed to R Chiquet-Ehrismann.
Tena, a Drosophila gene related to tenascin, shows selective transcript localization.
We report the identification and molecular characterization of tena*, a Drosophila gene located at 11A6-9 on the X-chromosome. The deduced protein of 782 amino acids contains eight tenascin-type EGF-like repeats not described in Drosophila before, but lacks the fibronectin type III repeats and the fibrinogen homology present in the vertebrate tenascin molecules. Tena codes for a large transcript which exhibits extremely long 5' and 3' untranslated regions. Tena transcripts show a specific perinuclear localization within cells and are mainly expressed in the central nervous system, in the brain and near muscle attachment sites during embryogenesis. During pupal stages, tena is detected in the eye. These expression patterns are reminiscent of those of vertebrate tenascin. Tenascin-type EGF-like sequences are also detected in other loci of Drosophila and in various other organisms, indicating the existence of a family of genes related to tenascin.
Amino Acid Sequence↗
Tenascin and other adhesion-modulating proteins in cancer.
A loss in cell-cell adhesion and an increase in cell motility are clearly prerequisites for the development of invasive tumors and metastasis. Since disseminating tumor cells have to interact with and migrate through extracellular matrices it is of interest to compare the composition of extracellular matrix proteins in normal and tumor tissues, in order to determine whether the extracellular matrix could be critically involved in affecting tumor cell adhesion and migration. The question will be addressed whether tumor extracellular matrix contains increased amounts of potentially antiadhesive extracellular matrix components and whether cells behave differently depending on the extracellular matrix they encounter. The results reviewed support the hypothesis that changes in the extracellular matrix and the cellular receptors are indeed important in the process of tumorigenesis.
Animals↗
Tenascin variants: ligands and expression.
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Animals↗
Tenascin function and regulation of expression.
Tenascin is a large hexameric extracellular matrix protein. Each subunit consists of a linear array of the following structural domains: an N-terminal cysteine-rich region and heptad repeats both involved in the oligomerization, followed by EGF-like repeats, fibronectin type III domains and a C-terminal globular domain homologous to fibrinogens. Depending on the species, the number of EGF-like repeats as well as of the fibronectin type III repeats differs. A model proposing a new nomenclature for the numbering of the fibronectin type III repeats is presented. It enables the assignment of corresponding repeats from different species and shows that for human tenascin several more alternatively spliced fibronectin type III repeats have been described than for chicken or mouse tenascin. Tenascin is generally classified as an anti-adhesive protein, since many cells do not adhere to tenascin or if they adhere they do not spread. The addition of tenascin can also lead to the loss of focal contacts in well spread cells. On the other hand growth cones adhere well to tenascin and a tenascin substrate can support neurite extension. Using recombinant fragments of tenascin we could identify an adhesive as well as an anti-adhesive region within one tenascin subunit. The major interest in tenascin was prompted by its interesting tissue distribution. Tenascin is often transiently expressed during organogenesis, tissue remodeling, cell migration and the development of the nervous system. We thus investigated possibilities to regulate tenascin expression in primary chick embryo fibroblast cultures.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Increased expression of tenascin in the dermis in scleroderma.
The expression of tenascin, a recently discovered extracellular matrix protein, was studied by immunohistochemical techniques in scleroderma skin and compared with its distribution in normal skin. In progressive systemic sclerosis, a marked increase in tenascin content was observed in the superficial reticular dermis. In localized scleroderma, the deposition of tenascin was increased both in the superficial and deep dermis of involved skin, whereas in clinically uninvolved skin the distribution of tenascin was the same as in normal control skin, i.e. the papillary dermis and peri-appendiceal zone. The distribution of tenascin did not strictly parallel that of fibronectin. These findings and the current knowledge of tenascin biology suggest that the overproduction of tenascin in scleroderma dermis could be secondary to stimulation of fibroblasts by immune cell-derived cytokines, or could be due to abnormal fibroblasts, or a subpopulation of fibroblasts, producing high levels of this extracellular matrix protein.
Adult↗
Isolation of chick tenascin variants and fragments. A C-terminal heparin-binding fragment produced by cleavage of the extra domain from the largest subunit splicing variant.
The extracellular-matrix glycoprotein, tenascin, consists of disulfide-linked subunits of 190, 200 and 230 kDa (the three splicing variants reported in chicken) and usually exists as a six-armed structure under the electron microscope. We used monoclonal antibodies to isolate and characterize different splicing variants and proteolytic fragments obtained from the native protein. Purified monomeric tenascin has a native molecular mass of 216 kDa and is structured as single arms. Tenascin fragments obtained by pepsin digestion bind to monoclonal antibody (mAb) TnM1 which is directed against epidermal-growth-factor-like repeats in the N-terminal half of all subunits. These fragments represent the thin proximal part of the tenascin arms and they are still partially linked to dimers and trimers via disulfide bridges. Using mAb Tn68, that reacts with a fibronectin-type-III repeat towards the C-terminus, a tenascin fragment, generated by treatment with pronase, can be isolated. Ultrastructurally, this fragment looks like the thicker distal part of the tenascin arms. Only the 230-kDa variant of tenascin gives rise to this distal fragment after cleavage within the alternatively spliced fibronectin-type-III repeats. Native tenascin and all fragments containing the distal part of its arms bind to heparin-agarose, whereas the proximal fragments do not. Oligomeric and monomeric tenascin inhibit fibronectin-mediated fibroblast spreading with comparable efficiency when added to the culture medium, while the proximal fragment has no effect. The distal fragment as well as reduced and alkylated tenascin are active in this assay, but only at higher molar concentrations when compared to the native protein.
Animals↗
Syndecan from embryonic tooth mesenchyme binds tenascin.
Syndecan is a cell surface heparan sulfate-rich proteoglycan found on various epithelial cells but also in some embryonic mesenchymal tissues. We have immunoisolated syndecan from embryonic tooth mesenchyme that appeared as a 250-300-kDa molecule (Kav = 0.3 in Sepharose 4B), containing only heparan sulfate side chains (Mr = 35,000). Northern analysis of whole tooth germs and tooth mesenchymes also revealed high expression of syndecan mRNAs (2.6 and 3.4 kilobases). In the binding assay utilizing nitrocellulose as a solid phase to immobilize matrix molecules, syndecan immunoisolated from tooth mesenchyme revealed binding to tenascin, and this interaction was shown to be mediated via heparan sulfate side chains. In contrast, syndecan from mouse mammary epithelial cells showed only weak interaction with tenascin. We propose that syndecan and tenascin may represent interactions of a cell surface receptor and a matrix ligand involved in mesenchymal cell condensation and differentiation during early organogenesis.
Animals↗
The human placenta: a model for tenascin expression.
Tenascin is a large glycoprotein of the extracellular matrix. Previous reports have demonstrated that it is associated with epithelial-mesenchymal interfaces and is expressed during embryonic and tumour development, wound healing, cell proliferation and it may be involved in immunomodulation. The human placenta shows numerous features related to these aspects. We have investigated the presence of tenascin in the human placenta throughout pregnancy by immunohistochemistry. We used monoclonal (mAb) and polyclonal (pAb) antibodies to tenascin, a mAb to fibrin, a pAb to fibrinogen, and the mAb Ki-67 as proliferation marker. Tenascin was highly expressed in the mesenchymal villi which are considered the basis of growth and differentiation of the villous trees. Moreover, fibrinoid deposits at the surfaces of the villous trees were always separated from the fetal stroma by tenascin. The stroma of villi encased in fibrinoid was also positive for tenascin. This glycoprotein was also expressed in the villous stroma directly apposed to cell islands and cell columns. In the proximal portions of both epithelial structures, cytotrophoblast was Ki-67 positive. These data show that tenascin is expressed during the development of the placenta, particularly in the mesenchymal villi, cell islands and cell columns. These structures are considered to be the proliferating units of the villous trees. Tenascin underlying fibrinoid deposits suggests that it also participates in repair mechanisms. Thus, in the human placenta tenascin expression can be correlated with villous growth, cell proliferation, and fibrinoid deposition. Its role in immunoprotection of fetal tissues in areas where syncytiotrophoblast as barrier is missing or damaged is discussed.
Cell Adhesion Molecules, Neuronal↗
Tenascin gene expression in rat liver and in rat liver cells. In vivo and in vitro studies.
Tenascin is a major glycoprotein constituent of the extracellular matrix with a strong affinity to fibronectin; its distribution is believed to be temporarily and spatially limited. Tenascin gene expression is increased during wound healing processes. As repair mechanisms in chronic liver diseases resemble wound healing we studied tenascin gene expression in rat liver and in isolated rat liver cells. In normal rat liver a tenascin specific antiserum stains sinusoidal cells with fiber-like prolongations, which at the same time are desmin-positive (ITO-cells). In the CCl4-acutely-damaged liver a strong tenascin staining is detected in cells located among the mononuclear cells of the inflammatory infiltrates in the areas of necrosis and in cells of the sinusoids. In CCl4-chronically-damaged liver a strong tenascin staining is demonstrable in the connective tissue septa. In both cases, many of the tenascin-positive cells can be identified as desmin-positive by means of the double-staining fluorescence technique. The wall of larger vessels is always tensacin-negative. The staining pattern obtained with a fibronectin-specific antiserum is somewhat comparable with that of tenascin but the vessel wall was positive. hepatocytes, Kupffer cells, ITO-cells and endothelial cells were isolated from rat liver and studied for their capacity to express the tenascin gene. Biosynthetically labeled tenascin was immunoprecipated from supernatants and cell lysates obtained from cultured ITO-cells and to a much lesser extent from intracellular lysates obtained from endothelial cells; its synthesis in ITO-cells increased during the time in culture. Tenascin was also identified immuno-cytochemically in increasing amount in ITO-cells in culture.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Changes in the cellular phenotype and extracellular matrix during progression of estrogen-induced mesenchymal kidney tumors in Syrian hamsters.
The cellular origin of estrogen-induced kidney tumors in male Syrian hamsters has been repeatedly the subject of controversy. Several authors have proposed that the tumors arise from proximal tubules, from a combination of tubular and interstitial stromal cells, or solely from interstitial cells. Because of the model character of this tumor for hormone-associated cancer, it was further investigated in this study with respect to morphology, enzyme and intermediate filament pattern, the expression of alpha-smooth muscle actin and the extracellular matrix proteins fibronectin and tenascin. These analyses were carried out with early and late tumors as well as metastases to determine possible changes in expression of biochemical parameters during the development and progression of this neoplasm. The enzyme histochemical and intermediate filament patterns were usually the same as those described previously for proliferative foci and early tumors, i.e. highly elevated activities of glucose-6-phosphate dehydrogenase, adenylate cyclase and alkaline phosphatase, a lack of glucose-6-phosphatase and gamma-glutamyltransferase and coexpression of vimentin and desmin, alpha-smooth muscle actin could not be detected in early lesions. In five of 24 advanced tumors inclusions of kidney tubules were found which showed various degrees of alteration in their morphology and enzyme histochemical pattern, but were often directly connected with tubular segments of normal appearance outside the tumor. Like the normal tubules, the enclosed tubular segments were strongly positive for cytokeratin but never expressed vimentin or desmin. Among the 24 tumors studied, two contained cysts which expressed cytokeratin and sometimes also vimentin but not desmin. The enzyme histochemistry of the cells lining the cysts was similar to that of the surrounding tumor mass, except adenylate cyclase was lacking and alkaline phosphatase was not uniformly distributed. In tumors containing cytokeratin-positive cysts, there often were cytokeratin-positive, vimentin-negative and desmin-negative tumor formations in close contact to these cysts. With the exception of cyst formation, the pattern of metastases were identical to that of the primary tumors. All large tumors and the main component of the metastases expressed vimentin, desmin and fibronectin. Mesothelia surrounding metastatic tumor complexes were positive for vimentin, desmin, alpha-smooth muscle actin, fibronectin, cytokeratin and tenascin. It was concluded from these and previous observations on early stages of tumor development that the estrogen-induced hamster kidney tumor originates from mesenchymal interstitial cells (probably pericytes) which may rarely acquire an epithelial phenotype by metaplastic transformation during tumor progression.
Adenylyl Cyclases↗
Anti-adhesive molecules of the extracellular matrix.
The prototype extracellular matrix glycoproteins had been identified on the basis of their activity in promoting cell adhesion and spreading. Recently, more and more evidence is accumulating that the reverse effect of extracellular matrix proteins, namely the inhibition of cell adhesion and spreading, may be equally important for proper cell function during morphogenesis and development. Several anti-adhesive proteins have been described and their mechanisms of action are being investigated.
Amino Acid Sequence↗
Tenascin variants: differential binding to fibronectin and distinct distribution in cell cultures and tissues.
In the chicken, three tenascin variants have been characterized that are generated by alternative splicing of 3 of its 11 fibronectin type III repeats. Using monoclonal antibodies that react with common regions versus extra repeats of tenascin, we could distinguish and separate tenascin variants and investigate their interaction with fibronectin using multiple experimental procedures. Interestingly, in all assays used the smallest tenascin variant bound more strongly to fibronectin than the larger ones. These biochemical data were paralleled by the observation that in chick embryo fibroblast cultures only the smallest form of tenascin could be detected in the fibronectin-rich extracellular matrix network laid down by the cells. Furthermore, each tissue present in adult chicken gizzard contained a distinct set of tenascin variants. Those tissues particularly rich in extracellular matrix, such as the tendon, contained the smallest tenascin only. Intermediate-sized tenascin was present in smooth muscle, whereas the largest form was exclusively detectable underneath the epithelial lining of the villi. Thus it appears that cell type-specific forms of tenascin exist that are appropriate for the functional requirements of the respective extracellular matrices.
Animals↗
Restrictin: a chick neural extracellular matrix protein involved in cell attachment co-purifies with the cell recognition molecule F11.
We report here the characterization of restrictin, a novel chick neural extracellular matrix glycoprotein associated with the cell recognition molecule F11. Immunoaffinity chromatography using monoclonal antibody 23-13 directed to restrictin yield a major relative molecular mass band at 170 x 10(3) and minor bands at 160, 180, 250 and 320 x 10(3) which are immunologically related to each other. Neural cells attach on immobilized restrictin in a short-term adhesion assay. This adhesion can be blocked specifically by monoclonal or polyclonal antibodies to restrictin but not by antibodies to F11 or by the peptide GRGDSP. Antibodies to restrictin do not interfere with the fasciculation of retinal axons and the isolated restrictin does not stimulate the outgrowth of axons. In the developing nervous system, restrictin is localized in very restricted regions and is found within areas of F11 expression. The timing and pattern of expression of restrictin and its cell attachment activity suggest that it participates in developmental events of the nervous system.
Animals↗
Differential expression of tenascin splicing variants in the chick gizzard and in cell cultures.
Tenascin is a large disulfide-linked hexameric extracellular matrix glycoprotein. It is a multidomain protein containing many repeated structural units such as heptad-, EGF-like-, and fibronectin type III repeats, as well as a homology to the globular domains of beta- and gamma-fibrinogen. In the chick embryo three major tenascin variants exist. They arise from one gene by alternative splicing of three of its 11 fibronectin type III repeats. Monoclonal antibodies against the alternatively spliced domains allowed us to study the expression of tenascin variants in tissue sections and in cell cultures. In the gizzard, the largest tenascin variant was only detected in the smooth muscle layer and the connective tissue below the epithelium of the villi, whereas the shortest tenascin variant was predominant in the tendons and the intramuscular connective tissue. Differential expression of tenascin variants was also obtained in cell cultures of chick embryo fibroblasts. Fetal calf serum equally stimulated the accumulation of all three tenascin variants, whereas after transformation with polyomavirus middle-T only the secretion of the largest tenascin variant was greatly enhanced.
Animals↗
Identification and characterization of a dimeric chicken fibronectin receptor. Subunit-specific monoclonal antibodies to the putative chicken alpha 5 beta 1 integrin.
A fibronectin receptor was isolated from chicken embryo fibroblasts using a cell-binding fragment of chicken fibronectin as an affinity matrix. The synthetic peptide GRGDSP specifically eluted the receptor, whereas the GRGESP control peptide was negative. The purified chicken receptor is a heterodimeric molecule as are all described mammalian integrins. It showed an RGD-dependent binding to fibronectin-coated wells after incorporation into liposomes. Monoclonal antibodies were raised against the two subunits of the receptor. Immunoprecipitations with the beta chain-specific monoclonal antibody U2 beta gave the same pattern of multiple bands as with the "avian integrin complex" specific monoclonal antibody JG22. In contrast, the alpha chain-specific monoclonal antibody U1 alpha only precipitated a dimeric fibronectin receptor. On immunoblots, U2 beta recognized the chicken gizzard integrin beta 1 chain, but U1 alpha did not cross-react with the alpha chain of gizzard integrin. Immunofluorescence labeling of cell cultures with U1 alpha revealed an exclusive colocalization with extracellular fibronectin fibrils, whereas U2 beta showed in addition, diffuse staining of the whole cell surfaces. The alpha chain-specific monoclonal antibody for the first time allowed us to exclusively detect the putative chicken alpha 5 beta 1 integrin among the many beta 1 integrin complexes present on chicken cells.
Amino Acid Sequence↗
Immunohistochemical study of the heterogeneity of tenascin distribution within the oral mucosa of the mouse.
Immunohistochemical labelling of adult mouse oral mucosa revealed a heterogeneous distribution of the extracellular matrix glycoprotein, tenascin. In masticatory mucosa (palate and gingiva), tenascin was selectively localized to the tips of connective tissue papillae, whilst in lining mucosa (ventral tongue, buccal, labial and vestibular) it was more uniformly distributed in the basement membrane. Tenascin was restricted to the connective tissue of specialized papillary tips in the dorsal lingual mucosa. The heterogeneous distribution of tenascin may be linked to mechanical function, proliferative organization within the overlying epithelium or to continuing epithelial-mesenchymal interactions.
Animals↗
What distinguishes tenascin from fibronectin?
Tenascin and fibronectin are two major extracellular matrix glycoproteins. They both consist of large disulfide-linked subunits composed of multiple structural domains. More than half of each molecule consists of so-called fibronectin type III repeats, but the other domains differ. Fibronectin is a dimer, whereas tenascin is a hexamer. Often fibronectin and tenascin are colocalized in tissues, but the occurrence of tenascin is much more restricted when compared with fibronectin. Tenascin is transiently expressed in many developing organs such as connective tissues, the mesenchyme of epithelial organs, and also the central and peripheral nervous systems, and it reappears in the stroma of many tumors. The distinctive and highly regulated expression of tenascin has provoked interest in trying to identify possible functions of tenascin in cell-cell and cell-substratum adhesion, cell migration, growth, and cell differentiation during morphogenesis.
Animals↗