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Mitotic motors coregulate microtubule patterns in axons and dendrites
Journal article   Open access   Peer reviewed

Mitotic motors coregulate microtubule patterns in axons and dendrites

Shen Lin, Mei Liu, Olga I Mozgova, Wenqian Yu and Peter W Baas
The Journal of neuroscience, v 32(40), pp 14033-14049
03 Oct 2012
DOI: https://doi.org/10.1523/JNEUROSCI.3070-12.2012
PMID: 23035110
Featured in Collection :   UN Sustainable Development Goals @ Drexel
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https://doi.org/10.1523/JNEUROSCI.3070-12.2012View
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Abstract

Cerebral Cortex - chemistry Nerve Tissue Proteins - physiology Spindle Apparatus - chemistry Antibodies, Monoclonal - pharmacology Kinesin - deficiency Microtubules - physiology Adrenergic Fibers - ultrastructure Rats Dendrites - ultrastructure Superior Cervical Ganglion - chemistry Superior Cervical Ganglion - cytology Cerebral Cortex - cytology Nerve Tissue Proteins - genetics Molecular Motor Proteins - physiology Animals Neurogenesis - physiology Nerve Tissue Proteins - isolation & purification Axons - ultrastructure Nerve Tissue Proteins - biosynthesis Kinesin - genetics Cell Polarity - physiology Kinesin - physiology Kinesin - antagonists & inhibitors Morphogenesis - physiology
Microtubules are nearly uniformly oriented in the axons of vertebrate neurons but are non-uniformly oriented in their dendrites. Studies to date suggest a scenario for establishing these microtubule patterns whereby microtubules are transported into the axon and nascent dendrites with plus-ends-leading, and then additional microtubules of the opposite orientation are transported into the developing dendrites. Here, we used contemporary tools to confirm that depletion of kinesin-6 (also called CHO1/MKLP1 or kif23) from rat sympathetic neurons causes a reduction in the appearance of minus-end-distal microtubules in developing dendrites, which in turn causes them to assume an axon-like morphology. Interestingly, we observed a similar phenomenon when we depleted kinesin-12 (also called kif15 or HKLP2). Both motors are best known for their participation in mitosis in other cell types, and both are enriched in the cell body and dendrites of neurons. Unlike kinesin-12, which is present throughout the neuron, kinesin-6 is barely detectable in the axon. Accordingly, depletion of kinesin-6, unlike depletion of kinesin-12, has no effect on axonal branching or navigation. Interestingly, depletion of either motor results in faster growing axons with greater numbers of mobile microtubules. Based on these observations, we posit a model whereby these two motors generate forces that attenuate the transport of microtubules with plus-ends-leading from the cell body into the axon. Some of these microtubules are not only prevented from moving into the axon but are driven with minus-ends-leading into developing dendrites. In this manner, these so-called "mitotic" motors coregulate the microtubule patterns of axons and dendrites.

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