Differentiation between Oppositely Oriented Microtubules Controls Polarized Neuronal Transport.

Differentiation between Oppositely Oriented Microtubules Controls Polarized Neuronal Transport.
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DOI:
10.1016/j.neuron.2017.11.018
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发表时间:
2017-12-20
期刊:
影响因子:
16.2
通讯作者:
Kapitein LC
Kapitein LC
中科院分区:
医学1区
文献类型:
--
作者:
Tas RP;Chazeau A;Cloin BMC;Lambers MLA;Hoogenraad CC;Kapitein LC

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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.
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