Cited by 250Mitochondrial Function and PathologyMicrotubule and mitosis dynamicsAutophagy in Disease and Therapy

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Kinesin-1–syntaphilin coupling mediates activity-dependent regulation of axonal mitochondrial transport

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Chen, Yanmin, Sheng, Zu-Hang·2013·Journal of Cell Biology

DOI 10.1083/jcb.201302040PMC PMC3718985

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Abstract

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 Ca2+ 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-Ca2+ 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.

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Authors: Chen, Y., & Sheng, Z.-H.
Affiliations: National Institutes of Health (US)
Corresponding author: Sheng, Zu-Hang
ORCID: Chen, Yanmin
Sheng, Zu-Hang
Venue: Journal of Cell Biology
Publisher: Rockefeller University Press
Published: 2013-07-15
Volume: 202
Issue: 2
Pages: 351-364
ISSN: 0021-9525 (ISSN-L)
1540-8140
DOI: 10.1083/jcb.201302040
PMC: PMC3718985
OpenAlex: W2059473497
Cited by: 250
References: 48
Citations by year: 2026: 15 · 2025: 18 · 2024: 15 · 2023: 19 · 2022: 16 · 2021: 28 · 2020: 25 · 2019: 18 · 2018: 13 · 2017: 24 · 2016: 17 · 2015: 18 · 2014: 20 · 2013: 4
FWCI: 8.82
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by-nc-sa
Locations: The Journal of Cell Biology (publishedVersion, cc-by-nc-sa)
Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
PubMed Central (publishedVersion, cc-by-nc-sa)
PubMed (publishedVersion)
Funders: National Institutes of Health
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
Keywords: syntaphilin, KIF5, kinesin-1, activity-dependent regulation, synaptic activity, calcium signaling, Rho GTPases, microtubule anchoring, synaptic mitochondria
MeSH terms: Animals, Axons, Biological Transport, Calcium, Carrier Proteins, Chlorocebus aethiops, Humans, Membrane Proteins, Mice, Inbred C57BL, Microtubule-Associated Proteins, Mitochondria, Nerve Tissue Proteins, Synaptic Transmission, Protein Binding, Kinesins, COS Cells, rho GTP-Binding Proteins, Protein Interaction Mapping, Mitochondrial Membranes, Mice, HEK293 Cells

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Kinesin-1–syntaphilin coupling mediates activity-dependent regulation of axonal mitochondrial transport

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