Document Detail


Mitotic motors coregulate microtubule patterns in axons and dendrites.
MedLine Citation:
PMID:  23035110     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Shen Lin; Mei Liu; Olga I Mozgova; Wenqian Yu; Peter W Baas
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  The Journal of neuroscience : the official journal of the Society for Neuroscience     Volume:  32     ISSN:  1529-2401     ISO Abbreviation:  J. Neurosci.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-04     Completed Date:  2013-01-17     Revised Date:  2013-07-11    
Medline Journal Info:
Nlm Unique ID:  8102140     Medline TA:  J Neurosci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  14033-49     Citation Subset:  IM    
Affiliation:
Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, Pennsylvania 19129, USA.
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MeSH Terms
Descriptor/Qualifier:
Adrenergic Fibers / ultrastructure
Animals
Antibodies, Monoclonal / pharmacology
Axons / ultrastructure*
Cell Polarity / physiology
Cerebral Cortex / chemistry,  cytology
Dendrites / ultrastructure*
Kinesin / antagonists & inhibitors,  deficiency,  genetics,  physiology
Microtubules / physiology*
Mitotic Spindle Apparatus / chemistry*
Molecular Motor Proteins / physiology*
Morphogenesis / physiology
Nerve Tissue Proteins / biosynthesis,  genetics,  isolation & purification,  physiology*
Neurogenesis / physiology
Rats
Superior Cervical Ganglion / chemistry,  cytology
Grant Support
ID/Acronym/Agency:
R01 NS028785/NS/NINDS NIH HHS; R56 NS028785/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Kif15 protein, rat; 0/Molecular Motor Proteins; 0/Nerve Tissue Proteins; EC 3.6.1.-/Kif11 protein, rat; EC 3.6.1.-/Kinesin
Comments/Corrections

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