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Kinesin-1–syntaphilin coupling mediates activity-dependent regulation of axonal mitochondrial transport
Axonal mitochondria are recruited to synaptic terminals in response to neuronal activity, but the mechanisms underlying activity-dependent regulation of mitochondrial transport are largely unknown. In this paper, using genetic mouse model combined with live imaging, we demonstrate that syntaphilin (...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3718985/ https://www.ncbi.nlm.nih.gov/pubmed/23857772 http://dx.doi.org/10.1083/jcb.201302040 |
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author | Chen, Yanmin Sheng, Zu-Hang |
author_facet | Chen, Yanmin Sheng, Zu-Hang |
author_sort | Chen, Yanmin |
collection | PubMed |
description | Axonal mitochondria are recruited to synaptic terminals in response to neuronal activity, but the mechanisms underlying activity-dependent regulation of mitochondrial transport are largely unknown. In this paper, using genetic mouse model combined with live imaging, we demonstrate that syntaphilin (SNPH) mediates the activity-dependent immobilization of axonal mitochondria through binding to KIF5. In vitro analysis showed that the KIF5–SNPH coupling inhibited the motor adenosine triphosphatase. Neuronal activity further recruited SNPH to axonal mitochondria. This motor-docking interplay was induced by Ca(2+) and synaptic activity and was necessary to establish an appropriate balance between motile and stationary axonal mitochondria. Deleting snph abolished the activity-dependent immobilization of axonal mitochondria. We propose an “Engine-Switch and Brake” model, in which SNPH acts both as an engine off switch by sensing mitochondrial Rho guanosine triphosphatase-Ca(2+) and as a brake by anchoring mitochondria to the microtubule track. Altogether, our study provides new mechanistic insight into the molecular interplay between motor and docking proteins, which arrests axonal mitochondrial transport in response to changes in neuronal activity. |
format | Online Article Text |
id | pubmed-3718985 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-37189852014-01-22 Kinesin-1–syntaphilin coupling mediates activity-dependent regulation of axonal mitochondrial transport Chen, Yanmin Sheng, Zu-Hang J Cell Biol Research Articles Axonal mitochondria are recruited to synaptic terminals in response to neuronal activity, but the mechanisms underlying activity-dependent regulation of mitochondrial transport are largely unknown. In this paper, using genetic mouse model combined with live imaging, we demonstrate that syntaphilin (SNPH) mediates the activity-dependent immobilization of axonal mitochondria through binding to KIF5. In vitro analysis showed that the KIF5–SNPH coupling inhibited the motor adenosine triphosphatase. Neuronal activity further recruited SNPH to axonal mitochondria. This motor-docking interplay was induced by Ca(2+) and synaptic activity and was necessary to establish an appropriate balance between motile and stationary axonal mitochondria. Deleting snph abolished the activity-dependent immobilization of axonal mitochondria. We propose an “Engine-Switch and Brake” model, in which SNPH acts both as an engine off switch by sensing mitochondrial Rho guanosine triphosphatase-Ca(2+) and as a brake by anchoring mitochondria to the microtubule track. Altogether, our study provides new mechanistic insight into the molecular interplay between motor and docking proteins, which arrests axonal mitochondrial transport in response to changes in neuronal activity. The Rockefeller University Press 2013-07-22 /pmc/articles/PMC3718985/ /pubmed/23857772 http://dx.doi.org/10.1083/jcb.201302040 Text en This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Research Articles Chen, Yanmin Sheng, Zu-Hang Kinesin-1–syntaphilin coupling mediates activity-dependent regulation of axonal mitochondrial transport |
title | Kinesin-1–syntaphilin coupling mediates activity-dependent regulation of axonal mitochondrial transport |
title_full | Kinesin-1–syntaphilin coupling mediates activity-dependent regulation of axonal mitochondrial transport |
title_fullStr | Kinesin-1–syntaphilin coupling mediates activity-dependent regulation of axonal mitochondrial transport |
title_full_unstemmed | Kinesin-1–syntaphilin coupling mediates activity-dependent regulation of axonal mitochondrial transport |
title_short | Kinesin-1–syntaphilin coupling mediates activity-dependent regulation of axonal mitochondrial transport |
title_sort | kinesin-1–syntaphilin coupling mediates activity-dependent regulation of axonal mitochondrial transport |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3718985/ https://www.ncbi.nlm.nih.gov/pubmed/23857772 http://dx.doi.org/10.1083/jcb.201302040 |
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