Tenascin-C at a glance Midwood, Kim S; Chiquet, Matthias; Tucker, Richard P ...
Journal of cell science,
12/2016, Letnik:
129, Številka:
23
Journal Article
Recenzirano
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Tenascin-C (TNC) is a hexameric, multimodular extracellular matrix protein with several molecular forms that are created through alternative splicing and protein modifications. It is highly conserved ...amongst vertebrates, and molecular phylogeny indicates that it evolved before fibronectin. Tenascin-C has many extracellular binding partners, including matrix components, soluble factors and pathogens; it also influences cell phenotype directly through interactions with cell surface receptors. Tenascin-C protein synthesis is tightly regulated, with widespread protein distribution in embryonic tissues, but restricted distribution of tenascin-C in adult tissues. Tenascin-C is also expressed de novo during wound healing or in pathological conditions, including chronic inflammation and cancer. First described as a modulator of cell adhesion, tenascin-C also directs a plethora of cell signaling and gene expression programs by shaping mechanical and biochemical cues within the cellular microenvironment. Exploitment of the pathological expression and function of tenascin-C is emerging as a promising strategy to develop new diagnostic, therapeutic and bioengineering tools. In this Cell Science at a Glance article and the accompanying poster we provide a succinct and comprehensive overview of the structural and functional features of tenascin-C and its potential roles in developing embryos and under pathological conditions.
This review summarizes the experimental evidence of tenascin-C/integrin interactions, emphasizing the identification of integrin binding sites and the effects of specific interactions on cell ...behavior. At least four integrins appear to bind to the third fibronectin-type 3 domain of tenascin-C: α9β1, αVβ3, α8β1 and αVβ6. The α9β1 integrin recognizes a highly conserved IDG motif in this domain, while the others recognize an RGD motif. There is also significant evidence that the collagen receptor α2β1 can bind to tenascin-C, but the interacting site is unknown. Tenascin-C interactions with α9β1 and αVβ3 can promote cell proliferation and interactions with αVβ3 can also inhibit apoptosis. Interactions with α7β1 integrin, which may bind to the alternatively spliced domain of tenascin-C, and α9β1 integrin are able to influence the differentiation of mesenchymal stem cells into the neuronal lineage. This illustrates the potential for using our knowledge of tenascins and their integrin receptors in stem cell-based therapies.
Disruption of teneurin expression results in abnormal neural networks, but just how teneurins support the development of the central nervous system remains an area of active research. This review ...summarizes some of what we know about the functions of the various domains of teneurins, the possible evolution of teneurins from a bacterial toxin, and the intriguing patterns of teneurin expression. Teneurins are a family of type-2 transmembrane proteins. The N-terminal intracellular domain can be processed and localized to the nucleus, but the significance of this nuclear localization is unknown. The extracellular domain of teneurins is largely composed of tyrosine-aspartic acid repeats that fold into a hollow barrel, and the C-terminal domains of teneurins are stuffed, and least partly, into the barrel. A 6-bladed beta-propeller is found at the other end of the barrel. The same arrangement-6-bladed beta-propeller, tyrosine-aspartic acid repeat barrel, and the C-terminal domain inside the barrel-is seen in toxic proteins from bacteria, and there is evidence that teneurins may have evolved from a gene encoding a prokaryotic toxin via horizontal gene transfer into an ancestral choanoflagellate. Patterns of teneurin expression are often, but not always, complementary. In the central nervous system, where teneurins are best studied, interconnected populations of neurons often express the same teneurin. For example, in the chicken embryo neurons forming the tectofugal pathway express teneurin-1, whereas neurons forming the thalamofugal pathway express teneurin-2. In
, zebrafish and mice, misexpression or knocking out teneurin expression leads to abnormal connections in the neural networks that normally express the relevant teneurin. Teneurins are also expressed in non-neuronal tissue during development, and in at least some regions the patterns of non-neuronal expression are also complementary. The function of teneurins outside the nervous system remains unclear.
For their full manifestation, tumors require support from the surrounding tumor microenvironment (TME), which includes a specific extracellular matrix (ECM), vasculature, and a variety of ...non-malignant host cells. Together, these components form a tumor-permissive niche that significantly differs from physiological conditions. While the TME helps to promote tumor progression, its special composition also provides potential targets for anti-cancer therapy. Targeting tumor-specific ECM molecules and stromal cells or disrupting aberrant mesenchyme-cancer communications might normalize the TME and improve cancer treatment outcome. The tenascins are a family of large, multifunctional extracellular glycoproteins consisting of four members. Although each have been described to be expressed in the ECM surrounding cancer cells, tenascin-C and tenascin-W are currently the most promising candidates for exploitability and clinical use as they are highly expressed in various tumor stroma with relatively low abundance in healthy tissues. Here, we review what is known about expression of all four tenascin family members in tumors, followed by a more thorough discussion on tenascin-C and tenascin-W focusing on their oncogenic functions and their potential as diagnostic and/or targetable molecules for anti-cancer treatment purposes.
To determine the sound environment of preterm infants cared for in the NICU and to test the hypothesis that infants exposed to more adult language will make more vocalizations.
This was a prospective ...cohort study of 36 infants who had a birth weight of ≤1250 g. Sixteen-hour recordings of the infant sound environment were made in the NICU from a digital language processor at 32 and 36 weeks' postmenstrual age. Adult word counts, infant vocalizations, and conversational turns were analyzed.
Infant vocalizations are present as early as 32 weeks. Both adult word counts per hour and infant vocalizations per hour increase significantly between 32 and 36 weeks. Infant exposure to language as a percentage of time was small but increased significantly. When a parent was present, infants had significantly more conversational turns per hour than when a parent was not present at both 32 and 36 weeks (P < .0001).
Preterm infants begin to make vocalizations at least 8 weeks before their projected due date and significantly increase their number of vocalizations over time. Although infant exposure to language increased over time, adult language accounted for only a small percentage of the sounds to which an infant is exposed in the NICU. Exposure to parental talk was a significantly stronger predictor of infant vocalizations at 32 weeks and conversational turns at 32 and 36 weeks than language from other adults. These findings highlight the powerful impact that parent talk has on the appearance and increment of vocalizations in preterm infants in the NICU.
The evolution of extracellular matrix Ozbek, Suat; Balasubramanian, Prakash G; Chiquet-Ehrismann, Ruth ...
Molecular biology of the cell,
12/2010, Letnik:
21, Številka:
24
Journal Article
Recenzirano
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We present a perspective on the molecular evolution of the extracellular matrix (ECM) in metazoa that draws on research publications and data from sequenced genomes and expressed sequence tag ...libraries. ECM components do not function in isolation, and the biological ECM system or "adhesome" also depends on posttranslational processing enzymes, cell surface receptors, and extracellular proteases. We focus principally on the adhesome of internal tissues and discuss its origins at the dawn of the metazoa and the expansion of complexity that occurred in the chordate lineage. The analyses demonstrate very high conservation of a core adhesome that apparently evolved in a major wave of innovation in conjunction with the origin of metazoa. Integrin, CD36, and certain domains predate the metazoa, and some ECM-related proteins are identified in choanoflagellates as predicted sequences. Modern deuterostomes and vertebrates have many novelties and elaborations of ECM as a result of domain shuffling, domain innovations and gene family expansions. Knowledge of the evolution of metazoan ECM is important for understanding how it is built as a system, its roles in normal tissues and disease processes, and has relevance for tissue engineering, the development of artificial organs, and the goals of synthetic biology.
Sex in zebrafish is not determined by a major chromosomal locus, but instead relies on a mechanism that is influenced by a germ cell-derived signal, as animals that lack germ cells, or specifically ...oocytes, develop as phenotypic males. These data suggest that during primary sex determination, an oocyte-derived signal acts on the bipotential somatic gonad to promote the female-specific program. However, it is not known if germ cells are required only during the primary sex-determining window, or if they are required throughout adult life to maintain the female sexual phenotype. Here, we show that while wild-type zebrafish do not switch sex as adults, germ cell-depleted adult females readily convert to a male phenotype. Notably, when oocytes are depleted, but germline stem cells remain, adult females sex-revert to sperm-producing males, indicating that a germ cell-derived signal acts on the somatic gonad to promote female development directly or indirectly by repressing male-specific gene expression. These results also confirm that signals from the somatic gonad in turn ensure that the sex appropriate gamete is produced.
► Germ cell depletion in adult zebrafish females leads to sex reversal. ► Sex reversed fish are both phenotypically and behaviorally male. ► Partial germ cell depletion in adult female fish results in fertile males. ► Role of germ cells in maintaining female sex may be conserved in teleost fish.
Tenascins are extracellular matrix proteins with distinct spatial and temporal expression during development, tissue homeostasis and disease. Based on their expression patterns and knockout ...phenotypes an important role of tenascins in tissue formation, cell adhesion modulation, regulation of proliferation and differentiation has been demonstrated. All of these features are of importance in stem cell niches where a precise regulation of growth versus differentiation has to be guaranteed. In this review we summarize the expression and possible functions of tenascins in neural, epithelial and osteogenic stem cell niches during normal development and organ turnover, in the hematopoietic and pro-inflammatory niche as well as in the metastatic niche during cancer progression.
•The function of tenascins in normal and pathological stem cell niches is summarized.•Tenascin-C and -R influence neural stem cell migration and differentiation•Tenascin-C and -W are present in stem cell niches of the limbus, whisker and bone.•Tenascin-C plays a role in the hematopoietic and lymphoid progenitor niche.•Tenascin-C is a crucial component of the angiogenic and metastatic niche in cancer.
Thrombospondins (TSPs) are multidomain, calcium-binding glycoproteins that have wide-ranging roles in vertebrates in cell interactions, extracellular matrix (ECM) organisation, angiogenesis, tissue ...remodelling, synaptogenesis, and also in musculoskeletal and cardiovascular functions. Land animals encode five TSPs, which assembly co-translationally either as trimers (subgroup A) or pentamers (subgroup B). The vast majority of research has focused on this canonical TSP family, which evolved through the whole-genome duplications that took place early in the vertebrate lineage. With benefit of the growth in genome- and transcriptome-predicted proteomes of a much wider range of animal species, examination of TSPs throughout metazoan phyla has revealed extensive conservation of subgroup B-type TSPs in invertebrates. In addition, these searches established that canonical TSPs are, in fact, one branch within a TSP superfamily that includes other clades designated mega-TSPs, sushi-TSPs and poriferan-TSPs. Despite the apparent simplicity of poriferans and cnidarians as organisms, these phyla encode a greater diversity of TSP superfamily members than vertebrates. We discuss here the molecular characteristics of the TSP superfamily members, current knowledge of their expression profiles and functions in invertebrates, and models for the evolution of this complex ECM superfamily.
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