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ALS-Linked Mutations Enlarge TDP-43-Enriched Neuronal RNA Granules in the Dendritic Arbor
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| Zeitschriftentitel: | The Journal of Neuroscience |
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| Personen und Körperschaften: | , , , , , , , , , |
| In: | The Journal of Neuroscience, 34, 2014, 12, S. 4167-4174 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
Society for Neuroscience
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| Schlagwörter: |
| author_facet |
Liu-Yesucevitz, LiQun Lin, Amy Y. Ebata, Atsushi Boon, Joon Y. Reid, Whitney Xu, Ya-Fei Kobrin, Kendra Murphy, George J. Petrucelli, Leonard Wolozin, Benjamin Liu-Yesucevitz, LiQun Lin, Amy Y. Ebata, Atsushi Boon, Joon Y. Reid, Whitney Xu, Ya-Fei Kobrin, Kendra Murphy, George J. Petrucelli, Leonard Wolozin, Benjamin |
|---|---|
| author |
Liu-Yesucevitz, LiQun Lin, Amy Y. Ebata, Atsushi Boon, Joon Y. Reid, Whitney Xu, Ya-Fei Kobrin, Kendra Murphy, George J. Petrucelli, Leonard Wolozin, Benjamin |
| spellingShingle |
Liu-Yesucevitz, LiQun Lin, Amy Y. Ebata, Atsushi Boon, Joon Y. Reid, Whitney Xu, Ya-Fei Kobrin, Kendra Murphy, George J. Petrucelli, Leonard Wolozin, Benjamin The Journal of Neuroscience ALS-Linked Mutations Enlarge TDP-43-Enriched Neuronal RNA Granules in the Dendritic Arbor General Neuroscience |
| author_sort |
liu-yesucevitz, liqun |
| spelling |
Liu-Yesucevitz, LiQun Lin, Amy Y. Ebata, Atsushi Boon, Joon Y. Reid, Whitney Xu, Ya-Fei Kobrin, Kendra Murphy, George J. Petrucelli, Leonard Wolozin, Benjamin 0270-6474 1529-2401 Society for Neuroscience General Neuroscience http://dx.doi.org/10.1523/jneurosci.2350-13.2014 <jats:p>Trans-activating response region (TAR) DNA-binding protein of 43 kDa (TDP-43) is an RNA-binding protein that is mutated in familial amyotrophic lateral sclerosis (ALS). Disease-linked mutations in TDP-43 increase the tendency of TDP-43 to aggregate, leading to a corresponding increase in formation of stress granules, cytoplasmic protein/RNA complexes that form in response to stress. Although the field has focused on stress granules, TDP-43 also forms other types of RNA granules. For example, TDP-43 is associated with RNA granules that are prevalent throughout the dendritic arbor in neurons. Because aggregation of TDP-43 is also important for the formation of these neuronal RNA granules, we hypothesized that disease-linked mutations might alter granule formation even in the absence of stress. We now report that ALS-linked mutations in TDP-43 (A315T and Q343R) increase the size of neuronal TDP-43 granules in the dendritic arbor of rat hippocampal neurons. The mutations correspondingly reduce the granule density, movement, and mobility of TDP-43 granules. Depolarization of rat hippocampal neurons with KCl stimulates TDP-43 granule migration into dendrites, but A315T and Q343R TDP-43 granules migrate shorter distances and into fewer dendrites than wild-type TDP-43. These findings highlight novel elements of TDP-43 biology that are affected by disease-linked mutations and suggest a neuronally selective mechanism through which TDP-43 mutations might elicit neuronal dysfunction.</jats:p> ALS-Linked Mutations Enlarge TDP-43-Enriched Neuronal RNA Granules in the Dendritic Arbor The Journal of Neuroscience |
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49 |
| title |
ALS-Linked Mutations Enlarge TDP-43-Enriched Neuronal RNA Granules in the Dendritic Arbor |
| title_unstemmed |
ALS-Linked Mutations Enlarge TDP-43-Enriched Neuronal RNA Granules in the Dendritic Arbor |
| title_full |
ALS-Linked Mutations Enlarge TDP-43-Enriched Neuronal RNA Granules in the Dendritic Arbor |
| title_fullStr |
ALS-Linked Mutations Enlarge TDP-43-Enriched Neuronal RNA Granules in the Dendritic Arbor |
| title_full_unstemmed |
ALS-Linked Mutations Enlarge TDP-43-Enriched Neuronal RNA Granules in the Dendritic Arbor |
| title_short |
ALS-Linked Mutations Enlarge TDP-43-Enriched Neuronal RNA Granules in the Dendritic Arbor |
| title_sort |
als-linked mutations enlarge tdp-43-enriched neuronal rna granules in the dendritic arbor |
| topic |
General Neuroscience |
| url |
http://dx.doi.org/10.1523/jneurosci.2350-13.2014 |
| publishDate |
2014 |
| physical |
4167-4174 |
| description |
<jats:p>Trans-activating response region (TAR) DNA-binding protein of 43 kDa (TDP-43) is an RNA-binding protein that is mutated in familial amyotrophic lateral sclerosis (ALS). Disease-linked mutations in TDP-43 increase the tendency of TDP-43 to aggregate, leading to a corresponding increase in formation of stress granules, cytoplasmic protein/RNA complexes that form in response to stress. Although the field has focused on stress granules, TDP-43 also forms other types of RNA granules. For example, TDP-43 is associated with RNA granules that are prevalent throughout the dendritic arbor in neurons. Because aggregation of TDP-43 is also important for the formation of these neuronal RNA granules, we hypothesized that disease-linked mutations might alter granule formation even in the absence of stress. We now report that ALS-linked mutations in TDP-43 (A315T and Q343R) increase the size of neuronal TDP-43 granules in the dendritic arbor of rat hippocampal neurons. The mutations correspondingly reduce the granule density, movement, and mobility of TDP-43 granules. Depolarization of rat hippocampal neurons with KCl stimulates TDP-43 granule migration into dendrites, but A315T and Q343R TDP-43 granules migrate shorter distances and into fewer dendrites than wild-type TDP-43. These findings highlight novel elements of TDP-43 biology that are affected by disease-linked mutations and suggest a neuronally selective mechanism through which TDP-43 mutations might elicit neuronal dysfunction.</jats:p> |
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| author | Liu-Yesucevitz, LiQun, Lin, Amy Y., Ebata, Atsushi, Boon, Joon Y., Reid, Whitney, Xu, Ya-Fei, Kobrin, Kendra, Murphy, George J., Petrucelli, Leonard, Wolozin, Benjamin |
| author_facet | Liu-Yesucevitz, LiQun, Lin, Amy Y., Ebata, Atsushi, Boon, Joon Y., Reid, Whitney, Xu, Ya-Fei, Kobrin, Kendra, Murphy, George J., Petrucelli, Leonard, Wolozin, Benjamin, Liu-Yesucevitz, LiQun, Lin, Amy Y., Ebata, Atsushi, Boon, Joon Y., Reid, Whitney, Xu, Ya-Fei, Kobrin, Kendra, Murphy, George J., Petrucelli, Leonard, Wolozin, Benjamin |
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| description | <jats:p>Trans-activating response region (TAR) DNA-binding protein of 43 kDa (TDP-43) is an RNA-binding protein that is mutated in familial amyotrophic lateral sclerosis (ALS). Disease-linked mutations in TDP-43 increase the tendency of TDP-43 to aggregate, leading to a corresponding increase in formation of stress granules, cytoplasmic protein/RNA complexes that form in response to stress. Although the field has focused on stress granules, TDP-43 also forms other types of RNA granules. For example, TDP-43 is associated with RNA granules that are prevalent throughout the dendritic arbor in neurons. Because aggregation of TDP-43 is also important for the formation of these neuronal RNA granules, we hypothesized that disease-linked mutations might alter granule formation even in the absence of stress. We now report that ALS-linked mutations in TDP-43 (A315T and Q343R) increase the size of neuronal TDP-43 granules in the dendritic arbor of rat hippocampal neurons. The mutations correspondingly reduce the granule density, movement, and mobility of TDP-43 granules. Depolarization of rat hippocampal neurons with KCl stimulates TDP-43 granule migration into dendrites, but A315T and Q343R TDP-43 granules migrate shorter distances and into fewer dendrites than wild-type TDP-43. These findings highlight novel elements of TDP-43 biology that are affected by disease-linked mutations and suggest a neuronally selective mechanism through which TDP-43 mutations might elicit neuronal dysfunction.</jats:p> |
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| spelling | Liu-Yesucevitz, LiQun Lin, Amy Y. Ebata, Atsushi Boon, Joon Y. Reid, Whitney Xu, Ya-Fei Kobrin, Kendra Murphy, George J. Petrucelli, Leonard Wolozin, Benjamin 0270-6474 1529-2401 Society for Neuroscience General Neuroscience http://dx.doi.org/10.1523/jneurosci.2350-13.2014 <jats:p>Trans-activating response region (TAR) DNA-binding protein of 43 kDa (TDP-43) is an RNA-binding protein that is mutated in familial amyotrophic lateral sclerosis (ALS). Disease-linked mutations in TDP-43 increase the tendency of TDP-43 to aggregate, leading to a corresponding increase in formation of stress granules, cytoplasmic protein/RNA complexes that form in response to stress. Although the field has focused on stress granules, TDP-43 also forms other types of RNA granules. For example, TDP-43 is associated with RNA granules that are prevalent throughout the dendritic arbor in neurons. Because aggregation of TDP-43 is also important for the formation of these neuronal RNA granules, we hypothesized that disease-linked mutations might alter granule formation even in the absence of stress. We now report that ALS-linked mutations in TDP-43 (A315T and Q343R) increase the size of neuronal TDP-43 granules in the dendritic arbor of rat hippocampal neurons. The mutations correspondingly reduce the granule density, movement, and mobility of TDP-43 granules. Depolarization of rat hippocampal neurons with KCl stimulates TDP-43 granule migration into dendrites, but A315T and Q343R TDP-43 granules migrate shorter distances and into fewer dendrites than wild-type TDP-43. These findings highlight novel elements of TDP-43 biology that are affected by disease-linked mutations and suggest a neuronally selective mechanism through which TDP-43 mutations might elicit neuronal dysfunction.</jats:p> ALS-Linked Mutations Enlarge TDP-43-Enriched Neuronal RNA Granules in the Dendritic Arbor The Journal of Neuroscience |
| spellingShingle | Liu-Yesucevitz, LiQun, Lin, Amy Y., Ebata, Atsushi, Boon, Joon Y., Reid, Whitney, Xu, Ya-Fei, Kobrin, Kendra, Murphy, George J., Petrucelli, Leonard, Wolozin, Benjamin, The Journal of Neuroscience, ALS-Linked Mutations Enlarge TDP-43-Enriched Neuronal RNA Granules in the Dendritic Arbor, General Neuroscience |
| title | ALS-Linked Mutations Enlarge TDP-43-Enriched Neuronal RNA Granules in the Dendritic Arbor |
| title_full | ALS-Linked Mutations Enlarge TDP-43-Enriched Neuronal RNA Granules in the Dendritic Arbor |
| title_fullStr | ALS-Linked Mutations Enlarge TDP-43-Enriched Neuronal RNA Granules in the Dendritic Arbor |
| title_full_unstemmed | ALS-Linked Mutations Enlarge TDP-43-Enriched Neuronal RNA Granules in the Dendritic Arbor |
| title_short | ALS-Linked Mutations Enlarge TDP-43-Enriched Neuronal RNA Granules in the Dendritic Arbor |
| title_sort | als-linked mutations enlarge tdp-43-enriched neuronal rna granules in the dendritic arbor |
| title_unstemmed | ALS-Linked Mutations Enlarge TDP-43-Enriched Neuronal RNA Granules in the Dendritic Arbor |
| topic | General Neuroscience |
| url | http://dx.doi.org/10.1523/jneurosci.2350-13.2014 |