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Microtubules provide directional cues for polarized axonal transport through interaction with kinesin motor head
Takao Nakata1, Nobutaka Hirokawa
1Department of Cell Biology and Anatomy, Graduate School of Medicine, University of Tokyo, 7-3-1, Hongo, Tokyo, Japan 113-0033.
Abstract:
Post-Golgi carriers of various newly synthesized axonal membrane proteins, which possess kinesin (KIF5)-driven highly processive motility, were transported from the TGN directly to axons. We found that KIF5 has a preference to the microtubules in the initial segment of axon. Low dose paclitaxel treatment caused missorting of KIF5, as well as axonal membrane proteins to the tips of dendrites. Microtubules in the initial segment of axons showed a remarkably high affinity to EB1-YFP, which was known to bind the tips of growing microtubules. These findings revealed unique features of the microtubule cytoskeletons in the initial segment, and suggested that they provide directional information for polarized axonal transport.
Insights
Kinesin (KIF5) transports axonal proteins to axons. Microtubules in the axon initial segment guide this transport, with disruptions causing protein missorting to dendrites.
Area of Science:
- Cell Biology
- Neuroscience
- Molecular Motor Proteins
Background:
- Axonal membrane proteins are synthesized and transported from the trans-Golgi network (TGN).
- Kinesin (KIF5) is a motor protein responsible for the processive motility of these protein carriers.
- Polarized transport is crucial for neuronal function, directing proteins to specific cellular compartments.
Purpose of the Study:
- To investigate the role of microtubules in the initial segment of axons in directing protein transport.
- To understand the mechanism by which kinesin (KIF5) is targeted to axons.
- To examine the impact of microtubule disruption on protein localization.
Main Methods:
- Utilized live-cell imaging to observe the transport of axonal membrane proteins and kinesin (KIF5).
- Employed paclitaxel treatment to disrupt microtubule dynamics.
- Investigated microtubule-binding proteins such as EB1-YFP.
Main Results:
- Kinesin (KIF5) preferentially binds to microtubules in the axon initial segment.
- Disruption of microtubules with low-dose paclitaxel led to missorting of KIF5 and axonal proteins to dendrites.
- Microtubules in the axon initial segment exhibit high affinity for EB1-YFP, indicating active growth sites.
Conclusions:
- The microtubule cytoskeleton in the axon initial segment possesses unique properties that direct polarized axonal transport.
- These microtubule features provide directional cues for kinesin-driven protein delivery to axons.
- Aberrations in this system can lead to aberrant protein localization, impacting neuronal structure and function.