Restraint of presynaptic protein levels by Wnd/DLK signaling mediates synaptic defects associated with the kinesin-3 motor Unc-104
The kinesin-3 family member Unc-104/KIF1A is required for axonal transport of many presynaptic components to synapses, and mutation of this gene results in synaptic dysfunction in mice, flies and worms. Our studies at the Drosophila neuromuscular junction indicate that many synaptic defects in unc-1...
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doaj-79619f4a1fa4450f97a7863533408fc22021-05-05T13:48:47ZengeLife Sciences Publications LtdeLife2050-084X2017-09-01610.7554/eLife.24271Restraint of presynaptic protein levels by Wnd/DLK signaling mediates synaptic defects associated with the kinesin-3 motor Unc-104Jiaxing Li0Yao V Zhang1Elham Asghari Adib2Doychin T Stanchev3Xin Xiong4Susan Klinedinst5Pushpanjali Soppina6Thomas Robert Jahn7https://orcid.org/0000-0002-9266-6736Richard I Hume8Tobias M Rasse9Catherine A Collins10https://orcid.org/0000-0002-1608-6692Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, United StatesJunior Research Group Synaptic Plasticity, Hertie-Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany; Graduate School of Cellular and Molecular Neuroscience, University of Tübingen, Tübingen, GermanyDepartment of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, United StatesJunior Research Group Synaptic Plasticity, Hertie-Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany; Graduate School of Cellular and Molecular Neuroscience, University of Tübingen, Tübingen, GermanyDepartment of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, United StatesDepartment of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, United StatesDepartment of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, United StatesCHS Research Group Proteostasis in Neurodegenerative Disease, DKFZ Deutsches Krebsforschungszentrum, Heidelberg, GermanyDepartment of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, United StatesJunior Research Group Synaptic Plasticity, Hertie-Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany; CHS Research Group Proteostasis in Neurodegenerative Disease, DKFZ Deutsches Krebsforschungszentrum, Heidelberg, GermanyDepartment of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, United StatesThe kinesin-3 family member Unc-104/KIF1A is required for axonal transport of many presynaptic components to synapses, and mutation of this gene results in synaptic dysfunction in mice, flies and worms. Our studies at the Drosophila neuromuscular junction indicate that many synaptic defects in unc-104-null mutants are mediated independently of Unc-104’s transport function, via the Wallenda (Wnd)/DLK MAP kinase axonal damage signaling pathway. Wnd signaling becomes activated when Unc-104’s function is disrupted, and leads to impairment of synaptic structure and function by restraining the expression level of active zone (AZ) and synaptic vesicle (SV) components. This action concomitantly suppresses the buildup of synaptic proteins in neuronal cell bodies, hence may play an adaptive role to stresses that impair axonal transport. Wnd signaling also becomes activated when pre-synaptic proteins are over-expressed, suggesting the existence of a feedback circuit to match synaptic protein levels to the transport capacity of the axon.https://elifesciences.org/articles/24271axonal transportkinesinsynapsesignalingstress response |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jiaxing Li Yao V Zhang Elham Asghari Adib Doychin T Stanchev Xin Xiong Susan Klinedinst Pushpanjali Soppina Thomas Robert Jahn Richard I Hume Tobias M Rasse Catherine A Collins |
spellingShingle |
Jiaxing Li Yao V Zhang Elham Asghari Adib Doychin T Stanchev Xin Xiong Susan Klinedinst Pushpanjali Soppina Thomas Robert Jahn Richard I Hume Tobias M Rasse Catherine A Collins Restraint of presynaptic protein levels by Wnd/DLK signaling mediates synaptic defects associated with the kinesin-3 motor Unc-104 eLife axonal transport kinesin synapse signaling stress response |
author_facet |
Jiaxing Li Yao V Zhang Elham Asghari Adib Doychin T Stanchev Xin Xiong Susan Klinedinst Pushpanjali Soppina Thomas Robert Jahn Richard I Hume Tobias M Rasse Catherine A Collins |
author_sort |
Jiaxing Li |
title |
Restraint of presynaptic protein levels by Wnd/DLK signaling mediates synaptic defects associated with the kinesin-3 motor Unc-104 |
title_short |
Restraint of presynaptic protein levels by Wnd/DLK signaling mediates synaptic defects associated with the kinesin-3 motor Unc-104 |
title_full |
Restraint of presynaptic protein levels by Wnd/DLK signaling mediates synaptic defects associated with the kinesin-3 motor Unc-104 |
title_fullStr |
Restraint of presynaptic protein levels by Wnd/DLK signaling mediates synaptic defects associated with the kinesin-3 motor Unc-104 |
title_full_unstemmed |
Restraint of presynaptic protein levels by Wnd/DLK signaling mediates synaptic defects associated with the kinesin-3 motor Unc-104 |
title_sort |
restraint of presynaptic protein levels by wnd/dlk signaling mediates synaptic defects associated with the kinesin-3 motor unc-104 |
publisher |
eLife Sciences Publications Ltd |
series |
eLife |
issn |
2050-084X |
publishDate |
2017-09-01 |
description |
The kinesin-3 family member Unc-104/KIF1A is required for axonal transport of many presynaptic components to synapses, and mutation of this gene results in synaptic dysfunction in mice, flies and worms. Our studies at the Drosophila neuromuscular junction indicate that many synaptic defects in unc-104-null mutants are mediated independently of Unc-104’s transport function, via the Wallenda (Wnd)/DLK MAP kinase axonal damage signaling pathway. Wnd signaling becomes activated when Unc-104’s function is disrupted, and leads to impairment of synaptic structure and function by restraining the expression level of active zone (AZ) and synaptic vesicle (SV) components. This action concomitantly suppresses the buildup of synaptic proteins in neuronal cell bodies, hence may play an adaptive role to stresses that impair axonal transport. Wnd signaling also becomes activated when pre-synaptic proteins are over-expressed, suggesting the existence of a feedback circuit to match synaptic protein levels to the transport capacity of the axon. |
topic |
axonal transport kinesin synapse signaling stress response |
url |
https://elifesciences.org/articles/24271 |
work_keys_str_mv |
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