Unique Function of Kinesin Kif5A in Localization of Mitochondria in Axons
- Campbell, P.D., Shen, K., Sapio, M.R., Glenn, T.D., Talbot, W.S., Marlow, F.L.
- The Journal of neuroscience : the official journal of the Society for Neuroscience 34: 14717-32 (Journal)
- Registered Authors
- Campbell, Philip, Glenn, Tom, Marlow, Florence, Talbot, William S.
- CMT, HSP, Kinesin, axon degeneration, mitochondria, sensory neuron
- MeSH Terms
- Axonal Transport/physiology
- Nerve Degeneration/genetics
- Nerve Degeneration/metabolism
- 25355224 Full text @ J. Neurosci.
Campbell, P.D., Shen, K., Sapio, M.R., Glenn, T.D., Talbot, W.S., Marlow, F.L. (2014) Unique Function of Kinesin Kif5A in Localization of Mitochondria in Axons. The Journal of neuroscience : the official journal of the Society for Neuroscience. 34:14717-32.
Mutations in Kinesin proteins (Kifs) are linked to various neurological diseases, but the specific and redundant functions of the vertebrate Kifs are incompletely understood. For example, Kif5A, but not other Kinesin-1 heavy-chain family members, is implicated in Charcot-Marie-Tooth disease (CMT) and Hereditary Spastic Paraplegia (HSP), but the mechanism of its involvement in the progressive axonal degeneration characteristic of these diseases is not well understood. We report that zebrafish kif5Aa mutants exhibit hyperexcitability, peripheral polyneuropathy, and axonal degeneration reminiscent of CMT and HSP. Strikingly, although kif5 genes are thought to act largely redundantly in other contexts, and zebrafish peripheral neurons express five kif5 genes, kif5Aa mutant peripheral sensory axons lack mitochondria and degenerate. We show that this Kif5Aa-specific function is cell autonomous and is mediated by its C-terminal tail, as only Kif5Aa and chimeric motors containing the Kif5Aa C-tail can rescue deficits. Finally, concurrent loss of the kinesin-3, kif1b, or its adaptor kbp, exacerbates axonal degeneration via a nonmitochondrial cargo common to Kif5Aa. Our results shed light on Kinesin complexity and reveal determinants of specific Kif5A functions in mitochondrial transport, adaptor binding, and axonal maintenance.
Genes / Markers
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Engineered Foreign Genes
Errata and Notes