Huntingtin recruits KIF1A to transport synaptic vesicle precursors along the mouse axon to support synaptic transmission and motor skill learning
Neurotransmitters are released at synapses by synaptic vesicles (SVs), which originate from SV precursors (SVPs) that have traveled along the axon. Because each synapse maintains a pool of SVs, only a small fraction of which are released, it has been thought that axonal transport of SVPs does not af...
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2023-07-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/81011 |
| _version_ | 1797773030305300480 |
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| author | Hélène Vitet Julie Bruyère Hao Xu Claire Séris Jacques Brocard Yah-Sé Abada Benoît Delatour Chiara Scaramuzzino Laurent Venance Frédéric Saudou |
| author_facet | Hélène Vitet Julie Bruyère Hao Xu Claire Séris Jacques Brocard Yah-Sé Abada Benoît Delatour Chiara Scaramuzzino Laurent Venance Frédéric Saudou |
| author_sort | Hélène Vitet |
| collection | DOAJ |
| description | Neurotransmitters are released at synapses by synaptic vesicles (SVs), which originate from SV precursors (SVPs) that have traveled along the axon. Because each synapse maintains a pool of SVs, only a small fraction of which are released, it has been thought that axonal transport of SVPs does not affect synaptic function. Here, studying the corticostriatal network both in microfluidic devices and in mice, we find that phosphorylation of the Huntingtin protein (HTT) increases axonal transport of SVPs and synaptic glutamate release by recruiting the kinesin motor KIF1A. In mice, constitutive HTT phosphorylation causes SV over-accumulation at synapses, increases the probability of SV release, and impairs motor skill learning on the rotating rod. Silencing KIF1A in these mice restored SV transport and motor skill learning to wild-type levels. Axonal SVP transport within the corticostriatal network thus influences synaptic plasticity and motor skill learning. |
| first_indexed | 2024-03-12T21:59:20Z |
| format | Article |
| id | doaj.art-b69d94da556b44d79eb205d590d95d58 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-03-12T21:59:20Z |
| publishDate | 2023-07-01 |
| publisher | eLife Sciences Publications Ltd |
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| series | eLife |
| spelling | doaj.art-b69d94da556b44d79eb205d590d95d582023-07-25T09:31:16ZengeLife Sciences Publications LtdeLife2050-084X2023-07-011210.7554/eLife.81011Huntingtin recruits KIF1A to transport synaptic vesicle precursors along the mouse axon to support synaptic transmission and motor skill learningHélène Vitet0Julie Bruyère1Hao Xu2Claire Séris3Jacques Brocard4https://orcid.org/0000-0002-0752-5737Yah-Sé Abada5Benoît Delatour6Chiara Scaramuzzino7https://orcid.org/0000-0001-9454-8701Laurent Venance8https://orcid.org/0000-0003-0738-1662Frédéric Saudou9https://orcid.org/0000-0001-6107-1046Univ. Grenoble Alpes, Inserm, U1216, CHU Grenoble Alpes, Grenoble Institut Neuroscience, Grenoble, FranceUniv. Grenoble Alpes, Inserm, U1216, CHU Grenoble Alpes, Grenoble Institut Neuroscience, Grenoble, FranceCenter for Interdisciplinary Research in Biology, College de France, CNRS, INSERM, Université PSL, Paris, FranceUniv. Grenoble Alpes, Inserm, U1216, CHU Grenoble Alpes, Grenoble Institut Neuroscience, Grenoble, FranceUniv. Grenoble Alpes, Inserm, U1216, CHU Grenoble Alpes, Grenoble Institut Neuroscience, Grenoble, FranceSorbonne Université, Institut du Cerveau, Paris Brain Institute, ICM, Inserm U1127, CNRS UMR7225, Paris, FranceSorbonne Université, Institut du Cerveau, Paris Brain Institute, ICM, Inserm U1127, CNRS UMR7225, Paris, FranceUniv. Grenoble Alpes, Inserm, U1216, CHU Grenoble Alpes, Grenoble Institut Neuroscience, Grenoble, FranceCenter for Interdisciplinary Research in Biology, College de France, CNRS, INSERM, Université PSL, Paris, FranceUniv. Grenoble Alpes, Inserm, U1216, CHU Grenoble Alpes, Grenoble Institut Neuroscience, Grenoble, FranceNeurotransmitters are released at synapses by synaptic vesicles (SVs), which originate from SV precursors (SVPs) that have traveled along the axon. Because each synapse maintains a pool of SVs, only a small fraction of which are released, it has been thought that axonal transport of SVPs does not affect synaptic function. Here, studying the corticostriatal network both in microfluidic devices and in mice, we find that phosphorylation of the Huntingtin protein (HTT) increases axonal transport of SVPs and synaptic glutamate release by recruiting the kinesin motor KIF1A. In mice, constitutive HTT phosphorylation causes SV over-accumulation at synapses, increases the probability of SV release, and impairs motor skill learning on the rotating rod. Silencing KIF1A in these mice restored SV transport and motor skill learning to wild-type levels. Axonal SVP transport within the corticostriatal network thus influences synaptic plasticity and motor skill learning.https://elifesciences.org/articles/81011synaptic vesicle precursorsaxonal transportmolecular motorsmotor skill learningcorticostriatal synapsemicrofluidics |
| spellingShingle | Hélène Vitet Julie Bruyère Hao Xu Claire Séris Jacques Brocard Yah-Sé Abada Benoît Delatour Chiara Scaramuzzino Laurent Venance Frédéric Saudou Huntingtin recruits KIF1A to transport synaptic vesicle precursors along the mouse axon to support synaptic transmission and motor skill learning eLife synaptic vesicle precursors axonal transport molecular motors motor skill learning corticostriatal synapse microfluidics |
| title | Huntingtin recruits KIF1A to transport synaptic vesicle precursors along the mouse axon to support synaptic transmission and motor skill learning |
| title_full | Huntingtin recruits KIF1A to transport synaptic vesicle precursors along the mouse axon to support synaptic transmission and motor skill learning |
| title_fullStr | Huntingtin recruits KIF1A to transport synaptic vesicle precursors along the mouse axon to support synaptic transmission and motor skill learning |
| title_full_unstemmed | Huntingtin recruits KIF1A to transport synaptic vesicle precursors along the mouse axon to support synaptic transmission and motor skill learning |
| title_short | Huntingtin recruits KIF1A to transport synaptic vesicle precursors along the mouse axon to support synaptic transmission and motor skill learning |
| title_sort | huntingtin recruits kif1a to transport synaptic vesicle precursors along the mouse axon to support synaptic transmission and motor skill learning |
| topic | synaptic vesicle precursors axonal transport molecular motors motor skill learning corticostriatal synapse microfluidics |
| url | https://elifesciences.org/articles/81011 |
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