VCP binding influences intracellular distribution of the slow Wallerian degeneration protein, Wld(S)
| Autor: | David J. A. Wyllie, Richard R. Ribchester, Michael P. Coleman, Thomas M. Wishart, Giacomo Morreale, Jane E. Haley, Bogdan Beirowski, Anna L. Wilbrey, Smith Trevor Stanley, Laura Conforti, Elisabetta Babetto, Thomas H. Gillingwater, Robert Adalbert |
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| Rok vydání: | 2007 |
| Předmět: |
Intracellular Fluid
Wallerian degeneration Cytoplasm Transgene Mutation Missense Cell Cycle Proteins Mice Transgenic Nerve Tissue Proteins Biology PC12 Cells Animals Genetically Modified Cellular and Molecular Neuroscience Mice In vivo Valosin Containing Protein medicine Animals Humans Axon Molecular Biology Cells Cultured Adenosine Triphosphatases Brain Chemistry Cell Biology medicine.disease Fusion protein In vitro Cell biology Rats Mice Inbred C57BL medicine.anatomical_structure nervous system Proteasome Wallerian Degeneration Neuroscience Intracellular HeLa Cells Protein Binding |
| Zdroj: | Molecular and cellular neurosciences. 38(3) |
| ISSN: | 1095-9327 |
| Popis: | Wallerian degeneration slow (Wld(S)) mice express a chimeric protein that delays axonal degeneration. The N-terminal domain (N70), which is essential for axonal protection in vivo, binds valosin-containing protein (VCP) and targets both Wld(S) and VCP to discrete nuclear foci. We characterized the formation, composition and localization of these potentially important foci. Missense mutations show that the N-terminal sixteen residues (N16) of Wld(S) are essential for both VCP binding and targeting Wld(S) to nuclear foci. Removing N16 abolishes foci, and VCP binding sequences from ataxin-3 or HrdI restore them. In vitro, these puncta co-localize with proteasome subunits. In vivo, Wld(S) assumes a range of nuclear distribution patterns, including puncta, and its neuronal expression and intranuclear distribution is region-specific and varies between spontaneous and transgenic Wld(S) models. We conclude that VCP influences Wld(S) intracellular distribution, and thus potentially its function, by binding within the N70 domain required for axon protection. |
| Databáze: | OpenAIRE |
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