Kinesin-5 is essential for growth-cone turning.

Kinesin-5 is essential for growth-cone turning.
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DOI:
10.1016/j.cub.2008.11.021
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发表时间:
2008-12-23
期刊:
Current biology : CB
影响因子:
--
通讯作者:
Baas PW
Baas PW
中科院分区:
其他
文献类型:
--
作者:
Nadar VC;Ketschek A;Myers KA;Gallo G;Baas PW

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驱动蛋白-5是一种也在神经元中表达的有丝分裂马达,抑制驱动蛋白-5会导致轴突生长更快,这是由于轴突轴中微管(MT)上的力发生变化。在这里,我们研究了驱动蛋白-5是否在生长锥引导中发挥作用。生长锥转向要求中心(C-)域中的MT在转向的方向上进入外围(P-)域。我们发现,在培养的神经元中抑制驱动蛋白-5可以防止MT在生长锥内极化,并使它们生长超过通常会使它们转向的线索。我们发现,驱动蛋白-5是丰富的过渡(T-)区的生长锥和驱动蛋白-5的优先磷酸化的侧相反的MT的入侵。此外,当生长锥遇到转向线索时,磷酸驱动蛋白-5甚至在生长锥转向之前极化。另外的研究表明,驱动蛋白-5部分地通过拮抗细胞质动力蛋白起作用,并且这些马达驱动的力与MT的动力学性质一起起作用以确定MT是否可以进入P结构域。我们建议,驱动蛋白-5允许MT选择性地侵入生长锥的一侧,反对他们进入另一侧。
Inhibition of kinesin-5, a mitotic motor also expressed in neurons, causes axons to grow faster due to alterations in the forces on the microtubules (MTs) in the axonal shaft. Here, we investigated whether kinesin-5 plays a role in growth cone guidance. Growth cone turning requires that MTs in the central (C-) domain enter the peripheral (P-) domain in the direction of the turn. We found that inhibition of kinesin-5 in cultured neurons prevents MTs from polarizing within growth cones and causes them to grow past cues that would normally cause them to turn. We found that kinesin-5 is enriched in the transition (T-) zone of the growth cone and that kinesin-5 is preferentially phosphorylated on the side opposite to the invasion of MTs. Moreover, when a growth cone encounters a turning cue, phospho-kinesin-5 polarizes even before the growth cone turns. Additional studies indicate that kinesin-5 works in part by antagonizing cytoplasmic dynein, and that these motor-driven forces function together with the dynamic properties of the MTs to determine whether MTs can enter the P-domain. We propose that kinesin-5 permits MTs to selectively invade one side of the growth cone by opposing their entry into the other side.
细胞质动力蛋白在微管和神经丝的轴突转运中的作用。
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