Unloading kinesin transported cargoes from the tubulin track via the inflammatory c‐Jun N‐terminal kinase pathway
- 26 October 2006
- journal article
- Published by Wiley in The FASEB Journal
- Vol. 20 (14) , 2573-2575
- https://doi.org/10.1096/fj.06-6679fje
Abstract
Axonal transport of mitochondria and synaptic vesicle precursors via kinesin motor proteins is essential to keep integrity of axons and synapses. Disturbance of axonal transport is an early sign of neuroinflammatory and neurodegenerative diseases. Treatment of cultured neurons by the inflammatory cytokine tumor necrosis factor-α (TNF) stimulated phosphorylation of c-Jun N-terminal kinase (JNK) in neurites. TNF treatment induced dissociation of the heavy chain kinesin family-5B (KIF5B) protein from tubulin in axons but not cell bodies as determined by lifetime-based Förster resonance energy transfer (FRET) analysis. Dissociation of KIF5B from tubulin after TNF treatment was dependent on JNK activity. Furthermore, TNF inhibited axonal transport of mitochondria and synaptophysin by reducing the mobile fraction via JNK. Thus, TNF produced by activated glial cells in inflammatory or degenerative neurological diseases acts on neurites by acting on the kinesin-tubulin complex and inhibits axonal mitochondria and...Keywords
Funding Information
- Deutsche Forschungsgemeinschaft
- European Commission (LSHM‐CT‐2005–018637)
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