The Experts below are selected from a list of 105 Experts worldwide ranked by ideXlab platform
Iva Greenwald - One of the best experts on this subject based on the ideXlab platform.
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Evidence for functional redundancy between C. elegans ADAM Proteins SUP-17/Kuzbanian and ADM-4/TACE
Developmental Biology, 2005Co-Authors: Sophie Jarriault, Iva GreenwaldAbstract:Abstract The ectodomain of LIN-12/Notch Proteins is cleaved and shed upon ligand binding. In Caenorhabditis elegans, genetic evidence has implicated SUP-17, the ortholog of Drosophila Kuzbanian and mammalian ADAM10, as the protease that mediates this event. In mammals, however, biochemical evidence has implicated TACE, a different ADAM Protein. We have investigated potential functional redundancy of sup-17 and the C. elegans ortholog of TACE, adm-4, by exploring their roles in cell fate decisions mediated by lin-12/Notch genes. We found that reduced adm-4 activity, like reduced sup-17 activity, suppresses an allele of glp-1 that encodes a constitutively active receptor. Furthermore, concomitant reduction of adm-4 and sup-17 activity causes the production of two anchor cells in the hermaphrodite gonad, instead of one—a phenotype associated with loss of lin-12 activity. Concomitant reduction of both sup-17 and adm-4 activity in hermaphrodites results in highly penetrant synthetic sterility, which appears to reflect a defect in the spermatheca. Expression of a truncated form of LIN-12 that mimics the product of ectodomain shedding rescues this fertility defect, suggesting that sup-17 and adm-4 may mediate ectodomain shedding of LIN-12 and/or GLP-1. Our results are consistent with the possibility that sup-17 and adm-4 are functionally redundant for at least a subset of LIN-12/Notch-mediated decisions in C. elegans.
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sup 17 a caenorhabditis elegans ADAM Protein related to drosophila kuzbanian and its role in lin 12 notch signalling
Development, 1997Co-Authors: Mark M Metzstein, Iva GreenwaldAbstract:LIN-12/NOTCH Proteins mediate cell-cell interactions that specify cell fates. Previous work suggested that sup-17 facilitates lin-12 signalling in Caenorhabditis elegans. Here, we show that sup-17 encodes a member of the ADAM family of metalloproteases. SUP-17 is highly similar to Drosophila KUZBANIAN, which functions in Drosophila neurogenesis, and the vertebrate ADAM10 Protein. Furthermore, we show by genetic analysis that the extracellular domain of LIN-12 appears to be necessary for sup-17 to facilitate lin-12 signalling and that sup-17 does not act downstream of lin-12. Finally, we show by cell ablation experiments that sup-17 can act cell autonomously to facilitate lin-12 activity. We discuss the implications of our observations for LIN-12/NOTCH signalling and how our results complement and extend results obtained from genetic analysis of kuz in Drosophila.
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SUP-17, a Caenorhabditis elegans ADAM Protein related to Drosophila KUZBANIAN, and its role in LIN-12/NOTCH signalling
Development, 1997Co-Authors: Mark M Metzstein, Iva GreenwaldAbstract:LIN-12/NOTCH Proteins mediate cell-cell interactions that specify cell fates. Previous work suggested that sup-17 facilitates lin-12 signalling in Caenorhabditis elegans. Here, we show that sup-17 encodes a member of the ADAM family of metalloproteases. SUP-17 is highly similar to Drosophila KUZBANIAN, which functions in Drosophila neurogenesis, and the vertebrate ADAM10 Protein. Furthermore, we show by genetic analysis that the extracellular domain of LIN-12 appears to be necessary for sup-17 to facilitate lin-12 signalling and that sup-17 does not act downstream of lin-12. Finally, we show by cell ablation experiments that sup-17 can act cell autonomously to facilitate lin-12 activity. We discuss the implications of our observations for LIN-12/NOTCH signalling and how our results complement and extend results obtained from genetic analysis of kuz in Drosophila.
Mark M Metzstein - One of the best experts on this subject based on the ideXlab platform.
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sup 17 a caenorhabditis elegans ADAM Protein related to drosophila kuzbanian and its role in lin 12 notch signalling
Development, 1997Co-Authors: Mark M Metzstein, Iva GreenwaldAbstract:LIN-12/NOTCH Proteins mediate cell-cell interactions that specify cell fates. Previous work suggested that sup-17 facilitates lin-12 signalling in Caenorhabditis elegans. Here, we show that sup-17 encodes a member of the ADAM family of metalloproteases. SUP-17 is highly similar to Drosophila KUZBANIAN, which functions in Drosophila neurogenesis, and the vertebrate ADAM10 Protein. Furthermore, we show by genetic analysis that the extracellular domain of LIN-12 appears to be necessary for sup-17 to facilitate lin-12 signalling and that sup-17 does not act downstream of lin-12. Finally, we show by cell ablation experiments that sup-17 can act cell autonomously to facilitate lin-12 activity. We discuss the implications of our observations for LIN-12/NOTCH signalling and how our results complement and extend results obtained from genetic analysis of kuz in Drosophila.
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SUP-17, a Caenorhabditis elegans ADAM Protein related to Drosophila KUZBANIAN, and its role in LIN-12/NOTCH signalling
Development, 1997Co-Authors: Mark M Metzstein, Iva GreenwaldAbstract:LIN-12/NOTCH Proteins mediate cell-cell interactions that specify cell fates. Previous work suggested that sup-17 facilitates lin-12 signalling in Caenorhabditis elegans. Here, we show that sup-17 encodes a member of the ADAM family of metalloproteases. SUP-17 is highly similar to Drosophila KUZBANIAN, which functions in Drosophila neurogenesis, and the vertebrate ADAM10 Protein. Furthermore, we show by genetic analysis that the extracellular domain of LIN-12 appears to be necessary for sup-17 to facilitate lin-12 signalling and that sup-17 does not act downstream of lin-12. Finally, we show by cell ablation experiments that sup-17 can act cell autonomously to facilitate lin-12 activity. We discuss the implications of our observations for LIN-12/NOTCH signalling and how our results complement and extend results obtained from genetic analysis of kuz in Drosophila.
Nicole S Sampson - One of the best experts on this subject based on the ideXlab platform.
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polymeric ADAM Protein mimics interrogate mammalian sperm egg binding
ChemBioChem, 2009Co-Authors: Nicole S SampsonAbstract:: The sperm Proteins ADAM2 and ADAM3, members of the ADAM family of Proteins, have been implicated in mammalian sperm-egg binding. However, elucidating their roles is complex because of the interdependence of ADAM Protein expression in the testis. Hence, multivalent probes containing the three-amino acid binding sequence of ADAM2, glutamate-cysteine-aspartate (ECD), and ADAM3, glutamine-cysteine-aspartate (QCD), were designed, synthesized, and tested to investigate gamete interactions. In this work, ECD polymer mimics were synthesized by ring-opening metathesis polymerization with a faster initiating ruthenium catalyst than previously used. Polymers containing 100 copies of the ECD peptide mimic were found to be the best inhibitors of fertilization. The multivalent QCD polymers were also tested as inhibitors of fertilization. The structure-activity profile was the same as ECD polymers, but the overall potency was lower. Both ECD and QCD polymers require the presence of beta(1) integrin to inhibit fertilization. Next, triblock ABA and ABC copolymers containing both ECD and QCD ligands were synthesized with 96 monomer spacers as their B blocks. Although these polymers had lower densities of ECD and QCD peptides, their potencies correlated with the potencies of their corresponding homopolymers. In addition, no synergy between ECD and QCD mimics was observed. All the data suggest that QCD and ECD bind to the same complex of Proteins that includes beta(1) integrin.
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A Facile Synthetic Method to Prepare Fluorescently Labeled ROMP Polymers
Organic Letters, 2004Co-Authors: Kenny S. Roberts, Nicole S SampsonAbstract:To probe the activities of sperm ADAM Protein (fertilinβ), we devised a general synthetic strategy to generate fluorescently labeled fertilinβ oligopeptide polymers. Immunofluorescence studies with these polymers demonstrated that fertilinβ polymers bind specifically to a Protein receptor on the mouse egg plasma membrane.
Silvio C E Tosatto - One of the best experts on this subject based on the ideXlab platform.
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a computational model of the lgi1 Protein suggests a common binding site for ADAM Proteins
PLOS ONE, 2011Co-Authors: Emanuela Leonardi, Giorgia Busolin, Simonetta Andreazza, Stefano Vanin, Carlo Nobile, Silvio C E TosattoAbstract:Mutations of human leucine-rich glioma inactivated (LGI1) gene encoding the epitempin Protein cause autosomal dominant temporal lateral epilepsy (ADTLE), a rare familial partial epileptic syndrome. The LGI1 gene seems to have a role on the transmission of neuronal messages but the exact molecular mechanism remains unclear. In contrast to other genes involved in epileptic disorders, epitempin shows no homology with known ion channel genes but contains two domains, composed of repeated structural units, known to mediate Protein-Protein interactions. A three dimensional in silico model of the two epitempin domains was built to predict the structure-function relationship and propose a functional model integrating previous experimental findings. Conserved and electrostatic charged regions of the model surface suggest a possible arrangement between the two domains and identifies a possible ADAM Protein binding site in the β-propeller domain and another Protein binding site in the leucine-rich repeat domain. The functional model indicates that epitempin could mediate the interaction between Proteins localized to different synaptic sides in a static way, by forming a dimer, or in a dynamic way, by binding Proteins at different times. The model was also used to predict effects of known disease-causing missense mutations. Most of the variants are predicted to alter Protein folding while several other map to functional surface regions. In agreement with experimental evidence, this suggests that non-secreted LGI1 mutants could be retained within the cell by quality control mechanisms or by altering interactions required for the secretion process.
Michael J Stern - One of the best experts on this subject based on the ideXlab platform.
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unc 71 a disintegrin and metalloprotease ADAM Protein regulates motor axon guidance and sex myoblast migration in c elegans
Development, 2003Co-Authors: Xun Huang, Peng Huang, Matthew K Robinson, Michael J SternAbstract:The migration of cells and growth cones is a process that is guided by extracellular cues and requires the controlled remodeling of the extracellular matrix along the migratory path. The ADAM Proteins are important regulators of cellular adhesion and recognition because they can combine regulated proteolysis with modulation of cell adhesion. We report that the C. elegans gene unc-71 encodes a unique ADAM with an inactive metalloprotease domain. Loss-of-function mutations in unc-71 cause distinct defects in motor axon guidance and sex myoblast migration. Many unc-71 mutations affect the disintegrin and the cysteine-rich domains, supporting a major function of unc-71 in cell adhesion. UNC-71 appears to be expressed in a selected set of cells. Genetic mosaic analysis and tissue-specific expression studies indicate that unc-71 acts in a cell non-autonomous manner for both motor axon guidance and sex myoblast migration. Finally, double mutant analysis of unc-71 with other axon guidance signaling molecules suggests that UNC-71 probably functions in a combinatorial manner with integrins and UNC-6/netrin to provide distinct axon guidance cues at specific choice points for motoneurons.
