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http://www.nature.com/natureneuroscience/
Web End = Tubulin tyrosination navigates the kinesin-1 motor domain to axons
2009 Nature America, Inc. All rights reserved.
2009 Nature America, Inc. All rights reserved.
2009 Nature America, Inc. All rights reserved.
Yoshiyuki Konishi1,2 & Mitsutoshi Setou1,2
Neurons form distinctive axonal and dendritic compartments that are important for directional signaling, but the mechanisms that discriminate between axons and dendrites remain elusive. Previous studies have demonstrated that the kinesin-1 motor domain is capable of distinguishing the axon from dendrites. Here we found that the amino acid substitutions in the beta5-loop8 region transformed truncated kinesin-1 from a uni-destination (that is, the axon-specic destination) to a bi-destination (that is, axons and dendrites) state. Furthermore, tyrosinated tubulins that are abundant in somatodendrites prevent the wild-type kinesin-1 from binding to microtubules, whereas the bi-destinationtype kinesin-1 does not have this inhibition. Consistently, inhibition of tubulin tyrosination in rat hippocampal neurons resulted in the distribution of truncated kinesin-1 in both axons and dendrites. Our study identies a molecular mechanism that discriminates the axonal microtubules from somatodendritic microtubules, as well as a previously unknown linkage between tubulin modication and polarized trafcking in neurons.
Axonal and dendritic morphologies are distinctly regulated to establish neuronal circuits via as-yet-unknown intrinsic cellular mechanisms1,2
and via extrinsic cues to the cell. Recent studies on the establishment of polarity in hippocampal neurons have identied signaling pathways that are crucial for determining axonal fate35. The factors involved in these pathways are either localized in future axons or excluded from axons. The underlying mechanisms by which polarity factors are localized asymmetrically in cells remain to be elucidated6.
Kinesin-driven anterograde transport along microtubules7 has been implicated in the polarized trafcking that occurs in mature neurons8,9.
Recent studies have indicated that it also involved in neuronal polarization1012. Conventional kinesin (kinesin-1) consists of a heavy chain (Kif5) dimer and regulatory light chains8,9,13. The heavy chain dimer
hydrolyzes ATP and uses the released energy to move along micro-tubules, whereas the carboxyl-terminal tail domain binds to its cargo13.
Previous studies have demonstrated that the tail domain is important in motor regulation. In the absence of bound cargo, the kinesin tail interacts with the motor domain and inhibits its activity14,15. In
neurons, Kif5 is detected both in...