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

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

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
Venue
Journal of Cell Biology
Published
2013-07-15
Volume
202
Issue
2
Pages
351-364
ISSN
  • 0021-9525 (ISSN-L)
  • 1540-8140
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
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
  • Health Sciences › Medicine › Epidemiology › 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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