Differentiation between Oppositely Oriented Microtubules Controls Polarized Neuronal Transport

Microtubules are essential for polarized transport in neurons, but how their organization guides motor proteins to axons or dendrites is unclear. Because different motors recognize distinct microtubule properties, we used optical nanoscopy to examine the relationship between microtubule orientations...

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Bibliographic Details
Published in:	Neuron (Cambridge, Mass.) Mass.), 2017-12, Vol.96 (6), p.1264-1271.e5
Main Authors:	Tas, Roderick P., Chazeau, Anaël, Cloin, Bas M.C., Lambers, Maaike L.A., Hoogenraad, Casper C., Kapitein, Lukas C.
Format:	Article
Language:	eng
Subjects:	Animals axon Axon guidance Axonal transport Axons Axons - physiology Bundles Cell cycle Cell Differentiation - physiology Cell Polarity - physiology Cytoskeleton Dendrites Dendrites - physiology Drosophila Insects Kinesin Kinesin - metabolism Localization microtubule orientation microtubule polarity Microtubule-Associated Proteins - metabolism Microtubules Microtubules - metabolism Models, Neurological Molecular motors motor proteins Nanotechnology neuronal polarity Neurons Neurons - cytology Neurons - physiology Optical properties Polarity polarized transport Protein Transport - physiology Proteins
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Summary:	Microtubules are essential for polarized transport in neurons, but how their organization guides motor proteins to axons or dendrites is unclear. Because different motors recognize distinct microtubule properties, we used optical nanoscopy to examine the relationship between microtubule orientations, stability, and modifications. Nanometric tracking of motors to super-resolve microtubules and determine their polarity revealed that in dendrites, stable and acetylated microtubules are mostly oriented minus-end out, while dynamic and tyrosinated microtubules are oriented oppositely. In addition, microtubules with similar orientations and modifications form bundles that bias transport. Importantly, because the plus-end-directed Kinesin-1 selectively interacts with acetylated microtubules, this organization guides this motor out of dendrites and into axons. In contrast, Kinesin-3 prefers tyrosinated microtubules and can enter both axons and dendrites. This separation of distinct microtubule subsets into oppositely oriented bundles constitutes a key architectural principle of the neuronal microtubule cytoskeleton that enables polarized sorting by different motor proteins. •Motor-based nanoscopy enables direct observation of microtubule (MT) polarity•In neurons, MTs organize into polarized bundles that locally bias transport•In dendrites, bundles of opposite orientation differ in stability and composition•Dendritic MTs bias Kinesin-1 transport toward the soma, ensuring axon selectivity Tas et al. use optical nanoscopy to show that dendritic microtubules of opposite orientation differ in stability and composition and recruit different motor proteins. This explains why some motor proteins can move into dendrites while others can only enter axons.
ISSN:	0896-6273 1097-4199