9 research outputs found
Human Endometrial CD98 Is Essential for Blastocyst Adhesion
BACKGROUND: Understanding the molecular basis of embryonic implantation is of great clinical and biological relevance. Little is currently known about the adhesion receptors that determine endometrial receptivity for embryonic implantation in humans. METHODS AND PRINCIPAL FINDINGS: Using two human endometrial cell lines characterized by low and high receptivity, we identified the membrane receptor CD98 as a novel molecule selectively and significantly associated with the receptive phenotype. In human endometrial samples, CD98 was the only molecule studied whose expression was restricted to the implantation window in human endometrial tissue. CD98 expression was restricted to the apical surface and included in tetraspanin-enriched microdomains of primary endometrial epithelial cells, as demonstrated by the biochemical association between CD98 and tetraspanin CD9. CD98 expression was induced in vitro by treatment of primary endometrial epithelial cells with human chorionic gonadotropin, 17-β-estradiol, LIF or EGF. Endometrial overexpression of CD98 or tetraspanin CD9 greatly enhanced mouse blastocyst adhesion, while their siRNA-mediated depletion reduced the blastocyst adhesion rate. CONCLUSIONS: These results indicate that CD98, a component of tetraspanin-enriched microdomains, appears to be an important determinant of human endometrial receptivity during the implantation window
Estrogen Receptor Alpha Is Expressed in Mesenteric Mesothelial Cells and Is Internalized in Caveolae upon Freund's Adjuvant Treatment
Transformation of epithelial cells into connective tissue cells (epithelial-mesenchymal transition, EMT) is a complex mechanism involved in tumor metastasis, and in normal embryogenesis, while type II EMT is mainly associated with inflammatory events and tissue regenaration. In this study we examined type II EMT at the ultrastructural and molecular level during the inflammatory process induced by Freund's adjuvant treatment in rat mesenteric mesothelial cells. We found that upon the inflammatory stimulus mesothelial cells lost contact with the basal lamina and with each other, and were transformed into spindle-shaped cells. These morphological changes were accompanied by release of interleukins IL-1alpha, -1beta and IL-6 and by secretion of transforming growth factor beta (TGF-beta) into the peritoneal cavity. Mesothelial cells also expressed estrogen receptor alpha (ER-alpha) as shown by immunolabeling at the light and electron microscopical levels, as well as by quantitative RT-PCR. The mRNA level of ER-alpha showed an inverse correlation with the secretion of TGF-beta. At the cellular and subcellular levels ER-alpha was colocalized with the coat protein caveolin-1 and was found in the plasma membrane of mesothelial cells, in caveolae close to multivesicular bodies (MVBs) or in the membrane of these organelles, suggesting that ER-alpha is internalized via caveola-mediated endocytosis during inflammation. We found asymmetric, thickened, electron dense areas on the limiting membrane of MVBs (MVB plaques) indicating that these sites may serve as platforms for collecting and organizing regulatory proteins. Our morphological observations and biochemical data can contribute to form a potential model whereby ER-alpha and its caveola-mediated endocytosis might play role in TGF-beta induced type II EMT in vivo
Beryllium Subphthalocyanines Self-Assembling Properties
Beryllium subphthalocyanines have been recently shown to be suitable candidates for photochemical devices if combined with appropriate donor systems. The ability of beryllium subphthalocyanines to self-assemble is explored for the first time by means of Density Functional Theory calculations. Free dimers of beryllium subphtalocyanine and their corresponding complexes with water and pyridine are computed at the wB97X-D/6-311+G(d,p) level of theory. In contrast with the behavior reported for beryllium phthalocyanines, for beryllium subphtalocyanines, beryllium-aza-nitrogen intermolecular interactions are observed, suggesting that these species are likely to self-assemble. Aggregates of related structures such as beryllium subporphyrazines with axial groups confirm the importance of hydrogen bonds in the stacking.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author
The sheddase activity of ADAM17/TACE is regulated by the tetraspanin CD9
ADAM17/TACE is a metalloproteinase
responsible for the shedding of the proinflammatory cytokine TNF-a and many other cell surface proteins involved in
development, cell adhesion, migration, differentiation, and
proliferation. Despite the important biological function of
ADAM17, the mechanisms of regulation of its metalloproteinase activity remain largely unknown. We report here that
the tetraspanin CD9 and ADAM17 partially co-localize on
the surface of endothelial and monocytic cells. In situ
proximity ligation, co-immunoprecipitation, crosslinking,
and pull-down experiments collectively demonstrate a direct
association between these molecules. Functional studies
reveal that treatment with CD9-specific antibodies or
neoexpression of CD9 exert negative regulatory effects on
ADAM17 sheddase activity. Conversely, CD9 silencing
increased the activity of ADAM17 against its substrates
TNF-a and ICAM-1. Taken together, our results show that
CD9 associates with ADAM17 and, through this interaction,
negatively regulates the sheddase activity of ADAM17s. This work was supported by
grants BFU2007-66443/BMC and BFU2010-19144/BMC from Ministerio de Ciencia e Innovación, a grant from Fundación de
Investigación Médica Mutua Madrileña and by RETICS Program
RD08/0075-RIER (Red de Inflamacio´n y Enfermedades Reumáticas)
from Instituto de Salud Carlos III (to C.C.), a grant from Fundación de
Investigación Médica Mutua Madrileña (to M.D.G.L.), and grants
PI080794 from Instituto de Salud Carlos III (to M.Y-M) and
SAF2007-60578 from Ministerio de Ciencia e Innovación (to
E.M.L.). M.D.G.L. was supported by a contract associated to grant
SAF2004-01715 from Ministerio de Ciencia e Innovacio´n. S.O. was
supported by an I3P predoctoral Fellowship from Consejo Superior de
Investigaciones Científicas (CSIC) and by a contract associated to
grant BFU2007-66443/BMC from Ministerio de Ciencia e Innovacio´n. A.G. has been supported by a predoctoral Fellowship from
Instituto de Salud Carlos III and by grant BFU2007-66443/BMC from
Ministerio de Ciencia e Innovación.Peer reviewe
Immunoassays for scarce tumour-antigens in exosomes: detection of the human NKG2D-Ligand, MICA, in tetraspanin-containing nanovesicles from melanoma
Vesiclepedia : a compendium for extracellular vesicles with continuous community annotation
Extracellular vesicles (EVs) are membraneous vesicles released by a variety of cells into their microenvironment. Recent studies have elucidated the role of EVs in intercellular communication, pathogenesis, drug, vaccine and gene-vector delivery, and as possible reservoirs of biomarkers. These findings have generated immense interest, along with an exponential increase in molecular data pertaining to EVs. Here, we describe Vesiclepedia, a manually curated compendium of molecular data (lipid, RNA, and protein) identified in different classes of EVs from more than 300 independent studies published over the past several years. Even though databases are indispensable resources for the scientific community, recent studies have shown that more than 50% of the databases are not regularly updated. In addition, more than 20% of the database links are inactive. To prevent such database and link decay, we have initiated a continuous community annotation project with the active involvement of EV researchers. The EV research community can set a gold standard in data sharing with Vesiclepedia, which could evolve as a primary resource for the field