Directed microtubule growth, +TIPs, and kinesin-2 are required for uniform microtubule polarity in dendrites.

Directed microtubule growth, +TIPs, and kinesin-2 are required for uniform microtubule polarity in dendrites.
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DOI:
10.1016/j.cub.2010.11.050
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发表时间:
2010-12-21
期刊:
影响因子:
9.2
通讯作者:
Rolls, Melissa M.
Rolls, Melissa M.
中科院分区:
生物学1区
文献类型:
--
作者:
Mattie, Floyd J.;Stackpole, Megan M.;Stone, Michelle C.;Clippard, Jessie R.;Rudnick, David A.;Qiu, Yijun;Tao, Juan;Allender, Dana L.;Parmar, Manpreet;Rolls, Melissa M.

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In many differentiated cells microtubules are organized into polarized noncentrosomal arrays, yet few mechanisms that control these arrays have been identified. For example, mechanisms that maintain microtubule polarity in the face of constant remodeling by dynamic instability are not known. Drosophila neurons contain uniform polarity minus-end-out microtubules in dendrites, which are often highly branched. As undirected microtubule growth through dendrite branch points jeopardizes uniform microtubule polarity, we have used this system to understand how cells can maintain dynamic arrays of polarized microtubules. We find that growing microtubules navigate dendrite branch points by turning the same way, towards the cell body, 98% of the time, and that growing microtubules track along stable microtubules towards their plus ends. Using RNAi and genetic approaches, we show that kinesin-2, and the +TIPS EB1 and APC, are required for uniform dendrite microtubule polarity. Moreover, the protein-protein interactions and localization of Apc2-GFP and Apc-RFP to branch points suggests these proteins work together at dendrite branches. The functional importance of this polarity mechanism is demonstrated by the failure of neurons with reduced kinesin-2 to regenerate an axon from a dendrite. We conclude that microtubule growth is directed at dendrite branch points, and that kinesin-2, APC and EB1 are likely to play a role in this process. We propose that is recruited to growing microtubules by +TIPS, and that the motor protein steers growing microtubules at branch points. This represents a newly discovered mechanism to maintain polarized arrays of microtubules.
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