Tau and spectraplakins promote synapse formation and maintenance through Jun kinase and neuronal trafficking
The mechanisms regulating synapse numbers during development and ageing are essential for normal brain function and closely linked to brain disorders including dementias. Using Drosophila, we demonstrate roles of the microtubule-associated protein Tau in regulating synapse numbers, thus unravelling...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2016-08-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/14694 |
| _version_ | 1811181019282276352 |
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| author | Andre Voelzmann Pilar Okenve-Ramos Yue Qu Monika Chojnowska-Monga Manuela del Caño-Espinel Andreas Prokop Natalia Sanchez-Soriano |
| author_facet | Andre Voelzmann Pilar Okenve-Ramos Yue Qu Monika Chojnowska-Monga Manuela del Caño-Espinel Andreas Prokop Natalia Sanchez-Soriano |
| author_sort | Andre Voelzmann |
| collection | DOAJ |
| description | The mechanisms regulating synapse numbers during development and ageing are essential for normal brain function and closely linked to brain disorders including dementias. Using Drosophila, we demonstrate roles of the microtubule-associated protein Tau in regulating synapse numbers, thus unravelling an important cellular requirement of normal Tau. In this context, we find that Tau displays a strong functional overlap with microtubule-binding spectraplakins, establishing new links between two different neurodegenerative factors. Tau and the spectraplakin Short Stop act upstream of a three-step regulatory cascade ensuring adequate delivery of synaptic proteins. This cascade involves microtubule stability as the initial trigger, JNK signalling as the central mediator, and kinesin-3 mediated axonal transport as the key effector. This cascade acts during development (synapse formation) and ageing (synapse maintenance) alike. Therefore, our findings suggest novel explanations for intellectual disability in Tau deficient individuals, as well as early synapse loss in dementias including Alzheimer’s disease. |
| first_indexed | 2024-04-11T09:12:23Z |
| format | Article |
| id | doaj.art-27432839e3b84319bd56809a3e8f00b2 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-11T09:12:23Z |
| publishDate | 2016-08-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-27432839e3b84319bd56809a3e8f00b22022-12-22T04:32:28ZengeLife Sciences Publications LtdeLife2050-084X2016-08-01510.7554/eLife.14694Tau and spectraplakins promote synapse formation and maintenance through Jun kinase and neuronal traffickingAndre Voelzmann0https://orcid.org/0000-0002-7682-5637Pilar Okenve-Ramos1https://orcid.org/0000-0002-7513-6557Yue Qu2https://orcid.org/0000-0002-2593-3654Monika Chojnowska-Monga3Manuela del Caño-Espinel4Andreas Prokop5https://orcid.org/0000-0001-8482-3298Natalia Sanchez-Soriano6https://orcid.org/0000-0002-6667-2817Faculty of Life Sciences, The University of Manchester, Manchester, United KingdomDepartment of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, United KingdomFaculty of Life Sciences, The University of Manchester, Manchester, United KingdomDepartment of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, United KingdomInstituto de Biología y Genética Molecular-Departamento de Bioquímica y Biología Molecular y Fisiología, Universidad de Valladolid-CSIC, Valladolid, SpainFaculty of Life Sciences, The University of Manchester, Manchester, United KingdomDepartment of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, United KingdomThe mechanisms regulating synapse numbers during development and ageing are essential for normal brain function and closely linked to brain disorders including dementias. Using Drosophila, we demonstrate roles of the microtubule-associated protein Tau in regulating synapse numbers, thus unravelling an important cellular requirement of normal Tau. In this context, we find that Tau displays a strong functional overlap with microtubule-binding spectraplakins, establishing new links between two different neurodegenerative factors. Tau and the spectraplakin Short Stop act upstream of a three-step regulatory cascade ensuring adequate delivery of synaptic proteins. This cascade involves microtubule stability as the initial trigger, JNK signalling as the central mediator, and kinesin-3 mediated axonal transport as the key effector. This cascade acts during development (synapse formation) and ageing (synapse maintenance) alike. Therefore, our findings suggest novel explanations for intellectual disability in Tau deficient individuals, as well as early synapse loss in dementias including Alzheimer’s disease.https://elifesciences.org/articles/14694axonsmicrotubulessynapsesneurodegenerationtransporttau |
| spellingShingle | Andre Voelzmann Pilar Okenve-Ramos Yue Qu Monika Chojnowska-Monga Manuela del Caño-Espinel Andreas Prokop Natalia Sanchez-Soriano Tau and spectraplakins promote synapse formation and maintenance through Jun kinase and neuronal trafficking eLife axons microtubules synapses neurodegeneration transport tau |
| title | Tau and spectraplakins promote synapse formation and maintenance through Jun kinase and neuronal trafficking |
| title_full | Tau and spectraplakins promote synapse formation and maintenance through Jun kinase and neuronal trafficking |
| title_fullStr | Tau and spectraplakins promote synapse formation and maintenance through Jun kinase and neuronal trafficking |
| title_full_unstemmed | Tau and spectraplakins promote synapse formation and maintenance through Jun kinase and neuronal trafficking |
| title_short | Tau and spectraplakins promote synapse formation and maintenance through Jun kinase and neuronal trafficking |
| title_sort | tau and spectraplakins promote synapse formation and maintenance through jun kinase and neuronal trafficking |
| topic | axons microtubules synapses neurodegeneration transport tau |
| url | https://elifesciences.org/articles/14694 |
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