Hyperphosphorylation and cleavage at D421 enhance tau secretion.
It is well established that tau pathology propagates in a predictable manner in Alzheimer's disease (AD). Moreover, tau accumulates in the cerebrospinal fluid (CSF) of AD's patients. The mechanisms underlying the propagation of tau pathology and its accumulation in the CSF remain to be elu...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3352936?pdf=render |
| _version_ | 1818270890335404032 |
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| author | Vanessa Plouffe Nguyen-Vi Mohamed Jessica Rivest-McGraw Johanne Bertrand Michel Lauzon Nicole Leclerc |
| author_facet | Vanessa Plouffe Nguyen-Vi Mohamed Jessica Rivest-McGraw Johanne Bertrand Michel Lauzon Nicole Leclerc |
| author_sort | Vanessa Plouffe |
| collection | DOAJ |
| description | It is well established that tau pathology propagates in a predictable manner in Alzheimer's disease (AD). Moreover, tau accumulates in the cerebrospinal fluid (CSF) of AD's patients. The mechanisms underlying the propagation of tau pathology and its accumulation in the CSF remain to be elucidated. Recent studies have reported that human tau was secreted by neurons and non-neuronal cells when it was overexpressed indicating that tau secretion could contribute to the spreading of tau pathology in the brain and could lead to its accumulation in the CSF. In the present study, we showed that the overexpression of human tau resulted in its secretion by Hela cells. The main form of tau secreted by these cells was cleaved at the C-terminal. Surprisingly, secreted tau was dephosphorylated at several sites in comparison to intracellular tau which presented a strong immunoreactivity to all phospho-dependent antibodies tested. Our data also revealed that phosphorylation and cleavage of tau favored its secretion by Hela cells. Indeed, the mimicking of phosphorylation at 12 sites known to be phosphorylated in AD enhanced tau secretion. A mutant form of tau truncated at D421, the preferential cleavage site of caspase-3, was also significantly more secreted than wild-type tau. Taken together, our results indicate that hyperphosphorylation and cleavage of tau by favoring its secretion could contribute to the propagation of tau pathology in the brain and its accumulation in the CSF. |
| first_indexed | 2024-12-12T21:17:28Z |
| format | Article |
| id | doaj.art-b45e93e0ccc849088cd3a00359c783f9 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-12T21:17:28Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-b45e93e0ccc849088cd3a00359c783f92022-12-22T00:11:42ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0175e3687310.1371/journal.pone.0036873Hyperphosphorylation and cleavage at D421 enhance tau secretion.Vanessa PlouffeNguyen-Vi MohamedJessica Rivest-McGrawJohanne BertrandMichel LauzonNicole LeclercIt is well established that tau pathology propagates in a predictable manner in Alzheimer's disease (AD). Moreover, tau accumulates in the cerebrospinal fluid (CSF) of AD's patients. The mechanisms underlying the propagation of tau pathology and its accumulation in the CSF remain to be elucidated. Recent studies have reported that human tau was secreted by neurons and non-neuronal cells when it was overexpressed indicating that tau secretion could contribute to the spreading of tau pathology in the brain and could lead to its accumulation in the CSF. In the present study, we showed that the overexpression of human tau resulted in its secretion by Hela cells. The main form of tau secreted by these cells was cleaved at the C-terminal. Surprisingly, secreted tau was dephosphorylated at several sites in comparison to intracellular tau which presented a strong immunoreactivity to all phospho-dependent antibodies tested. Our data also revealed that phosphorylation and cleavage of tau favored its secretion by Hela cells. Indeed, the mimicking of phosphorylation at 12 sites known to be phosphorylated in AD enhanced tau secretion. A mutant form of tau truncated at D421, the preferential cleavage site of caspase-3, was also significantly more secreted than wild-type tau. Taken together, our results indicate that hyperphosphorylation and cleavage of tau by favoring its secretion could contribute to the propagation of tau pathology in the brain and its accumulation in the CSF.http://europepmc.org/articles/PMC3352936?pdf=render |
| spellingShingle | Vanessa Plouffe Nguyen-Vi Mohamed Jessica Rivest-McGraw Johanne Bertrand Michel Lauzon Nicole Leclerc Hyperphosphorylation and cleavage at D421 enhance tau secretion. PLoS ONE |
| title | Hyperphosphorylation and cleavage at D421 enhance tau secretion. |
| title_full | Hyperphosphorylation and cleavage at D421 enhance tau secretion. |
| title_fullStr | Hyperphosphorylation and cleavage at D421 enhance tau secretion. |
| title_full_unstemmed | Hyperphosphorylation and cleavage at D421 enhance tau secretion. |
| title_short | Hyperphosphorylation and cleavage at D421 enhance tau secretion. |
| title_sort | hyperphosphorylation and cleavage at d421 enhance tau secretion |
| url | http://europepmc.org/articles/PMC3352936?pdf=render |
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