Untethering the Nuclear Envelope and Cytoskeleton: Biologically Distinct Dystonias Arising from a Common Cellular Dysfunction
Most cases of early onset DYT1 dystonia in humans are caused by a GAG deletion in the TOR1A gene leading to loss of a glutamic acid (ΔE) in the torsinA protein, which underlies a movement disorder associated with neuronal dysfunction without apparent neurodegeneration. Mutation/deletion of the gene...
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| Format: | Article |
| Language: | English |
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Wiley
2012-01-01
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| Series: | International Journal of Cell Biology |
| Online Access: | http://dx.doi.org/10.1155/2012/634214 |
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| author | Nadia A. Atai Scott D. Ryan Rashmi Kothary Xandra O. Breakefield Flávia C. Nery |
| author_facet | Nadia A. Atai Scott D. Ryan Rashmi Kothary Xandra O. Breakefield Flávia C. Nery |
| author_sort | Nadia A. Atai |
| collection | DOAJ |
| description | Most cases of early onset DYT1 dystonia in humans are caused by a GAG deletion in the TOR1A gene leading to loss of a glutamic acid (ΔE) in the torsinA protein, which underlies a movement disorder associated with neuronal dysfunction without apparent neurodegeneration. Mutation/deletion of the gene (Dst) encoding dystonin in mice results in a dystonic movement disorder termed dystonia musculorum, which resembles aspects of dystonia in humans. While torsinA and dystonin proteins do not share modular domain architecture, they participate in a similar function by modulating a structural link between the nuclear envelope and the cytoskeleton in neuronal cells. We suggest that through a shared interaction with the nuclear envelope protein nesprin-3α, torsinA and the neuronal dystonin-a2 isoform comprise a bridge complex between the outer nuclear membrane and the cytoskeleton, which is critical for some aspects of neuronal development and function. Elucidation of the overlapping roles of torsinA and dystonin-a2 in nuclear/endoplasmic reticulum dynamics should provide insights into the cellular mechanisms underlying the dystonic phenotype. |
| format | Article |
| id | doaj-art-34d3dbd809384fa9974ce898a6513b24 |
| institution | Kabale University |
| issn | 1687-8876 1687-8884 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | International Journal of Cell Biology |
| spelling | doaj-art-34d3dbd809384fa9974ce898a6513b242025-02-03T06:11:31ZengWileyInternational Journal of Cell Biology1687-88761687-88842012-01-01201210.1155/2012/634214634214Untethering the Nuclear Envelope and Cytoskeleton: Biologically Distinct Dystonias Arising from a Common Cellular DysfunctionNadia A. Atai0Scott D. Ryan1Rashmi Kothary2Xandra O. Breakefield3Flávia C. Nery4Neuroscience Center, Department of Neurology, Massachusetts General Hospital, East, Boston, MA 02114, USAOttawa Hospital Research Institute, Department of Cellular and Molecular Medicine, Ottawa, ON, KIH 8L6, CanadaOttawa Hospital Research Institute, Department of Cellular and Molecular Medicine, Ottawa, ON, KIH 8L6, CanadaNeuroscience Center, Department of Neurology, Massachusetts General Hospital, East, Boston, MA 02114, USANeuroscience Center, Department of Neurology, Massachusetts General Hospital, East, Boston, MA 02114, USAMost cases of early onset DYT1 dystonia in humans are caused by a GAG deletion in the TOR1A gene leading to loss of a glutamic acid (ΔE) in the torsinA protein, which underlies a movement disorder associated with neuronal dysfunction without apparent neurodegeneration. Mutation/deletion of the gene (Dst) encoding dystonin in mice results in a dystonic movement disorder termed dystonia musculorum, which resembles aspects of dystonia in humans. While torsinA and dystonin proteins do not share modular domain architecture, they participate in a similar function by modulating a structural link between the nuclear envelope and the cytoskeleton in neuronal cells. We suggest that through a shared interaction with the nuclear envelope protein nesprin-3α, torsinA and the neuronal dystonin-a2 isoform comprise a bridge complex between the outer nuclear membrane and the cytoskeleton, which is critical for some aspects of neuronal development and function. Elucidation of the overlapping roles of torsinA and dystonin-a2 in nuclear/endoplasmic reticulum dynamics should provide insights into the cellular mechanisms underlying the dystonic phenotype.http://dx.doi.org/10.1155/2012/634214 |
| spellingShingle | Nadia A. Atai Scott D. Ryan Rashmi Kothary Xandra O. Breakefield Flávia C. Nery Untethering the Nuclear Envelope and Cytoskeleton: Biologically Distinct Dystonias Arising from a Common Cellular Dysfunction International Journal of Cell Biology |
| title | Untethering the Nuclear Envelope and Cytoskeleton: Biologically Distinct Dystonias Arising from a Common Cellular Dysfunction |
| title_full | Untethering the Nuclear Envelope and Cytoskeleton: Biologically Distinct Dystonias Arising from a Common Cellular Dysfunction |
| title_fullStr | Untethering the Nuclear Envelope and Cytoskeleton: Biologically Distinct Dystonias Arising from a Common Cellular Dysfunction |
| title_full_unstemmed | Untethering the Nuclear Envelope and Cytoskeleton: Biologically Distinct Dystonias Arising from a Common Cellular Dysfunction |
| title_short | Untethering the Nuclear Envelope and Cytoskeleton: Biologically Distinct Dystonias Arising from a Common Cellular Dysfunction |
| title_sort | untethering the nuclear envelope and cytoskeleton biologically distinct dystonias arising from a common cellular dysfunction |
| url | http://dx.doi.org/10.1155/2012/634214 |
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