An evolutionary recent neuroepithelial cell adhesion function of huntingtin implicates ADAM10-Ncadherin
| Autor: | Marzia Tartari, Valentina Lo Sardo, Binia Drung, James A. Walker, Franco Cotelli, Barbara Vitali, Catarina Ramos, Scott Zeitlin, Anna Pistocchi, Elena Cattaneo, Germano Gaudenzi, Marta Valenza, Boris Schmidt, Luciano Conti, Chiara Zuccato, James F. Gusella, Michael A. Myre |
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| Rok vydání: | 2012 |
| Předmět: |
Embryo
Nonmammalian Huntingtin animal diseases Cellular differentiation Neuroepithelial Cells Apoptosis Hydroxamic Acids Cerebral Ventricles Animals Genetically Modified Discs Large Homolog 1 Protein Nestin ADAM10 Protein Mice Intermediate Filament Proteins Dictyostelium RNA Small Interfering Zebrafish Cells Cultured Neurons Genetics Huntingtin Protein biology General Neuroscience Brain Gene Expression Regulation Developmental Nuclear Proteins Cell Differentiation Dipeptides Cadherins Biological Evolution Neuroepithelial cell Drosophila melanogaster congenital hereditary and neonatal diseases and abnormalities Morpholines Green Fluorescent Proteins Nerve Tissue Proteins Wnt1 Protein Transfection mental disorders Cell Adhesion Animals Immunoprecipitation Hedgehog Proteins Cell adhesion Embryonic Stem Cells Body Patterning Analysis of Variance Tissue Inhibitor of Metalloproteinase-1 PAX2 Transcription Factor Membrane Proteins Zebrafish Proteins Embryo Mammalian biology.organism_classification nervous system diseases ADAM Proteins NFI Transcription Factors Neurulation nervous system Mutation Amyloid Precursor Protein Secretases Guanylate Kinases |
| Zdroj: | Nature Neuroscience. 15:713-721 |
| ISSN: | 1546-1726 1097-6256 |
| DOI: | 10.1038/nn.3080 |
| Popis: | The Huntington's disease gene product, huntingtin, is indispensable for neural tube formation, but its role is obscure. We studied neurulation in htt-null embryonic stem cells and htt-morpholino zebrafish embryos and found a previously unknown, evolutionarily recent function for this ancient protein. We found that htt was essential for homotypic interactions between neuroepithelial cells; it permitted neurulation and rosette formation by regulating metalloprotease ADAM10 activity and Ncadherin cleavage. This function was embedded in the N terminus of htt and was phenocopied by treatment of htt knockdown zebrafish with an ADAM10 inhibitor. Notably, in htt-null cells, reversion of the rosetteless phenotype occurred only with expression of evolutionarily recent htt heterologues from deuterostome organisms. Conversely, all of the heterologues that we tested, including htt from Drosophila melanogaster and Dictyostelium discoideum, exhibited anti-apoptotic activity. Thus, anti-apoptosis may have been one of htt’s ancestral function(s), but, in deuterostomes, htt evolved to acquire a unique regulatory activity for controlling neural adhesion via ADAM10-Ncadherin, with implications for brain evolution and development. |
| Databáze: | OpenAIRE |
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