Asymmetric endocytosis and remodeling of beta1-integrin adhesions during growth cone chemorepulsion by MAG.

Asymmetric endocytosis and remodeling of beta1-integrin adhesions during growth cone chemorepulsion by MAG.
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DOI:
10.1038/nn.2554
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发表时间:
2010-07
影响因子:
25
通讯作者:
Henley, John R.
Henley, John R.
中科院分区:
医学1区
文献类型:
--
作者:
Hines, Jacob H.;Abu-Rub, Mohammad;Henley, John R.

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髓磷脂释放的化学排斥因子可能损害轴突寻路和损伤后的神经再生。与侵袭性肿瘤细胞的趋化过程类似,我们发现非洲爪蟾脊髓神经元的轴突生长锥在髓鞘相关糖蛋白(MAG)诱导的化学排斥过程中调节整合素受体的功能分布。局灶性MAG梯度诱导极化内吞作用,并伴随排斥性转向过程中排斥侧上含β1-整合素和黏着斑蛋白的粘附的不对称损失。对称性β1-整联蛋白功能的丧失对于化学排斥是必要且充分的,其需要通过网格蛋白介导的内吞作用内化。排斥性Ca ~(2+)信号的诱导是β1-整合素快速内吞的必要条件。总之,这些研究结果确定β1-整合素作为一个重要的功能货物在钙依赖性快速内吞刺激的可扩散的指导线索。这种动态的重新分配允许生长锥快速调整其轴上的张力,这是启动趋化性转向的基本特征。
Gradients of chemorepellent factors released from myelin may impair axon pathfinding and neuro-regeneration after injury. Analogous to the process of chemotaxis in invasive tumor cells, we found that axonal growth cones of Xenopus spinal neurons modulate the functional distribution of integrin receptors during chemorepulsion induced by myelin-associated glycoprotein (MAG). A focal MAG gradient induced polarized endocytosis and concomitant asymmetric loss of β1-integrin and vinculin-containing adhesions on the repellent side during repulsive turning. Loss of symmetrical β1-integrin function was both necessary and sufficient for chemorepulsion, which required internalization by clathrin-mediated endocytosis. Induction of repulsive Ca2+ signals was necessary and sufficient for the stimulated rapid endocytosis of β1-integrin. Altogether, these findings identify β1-integrin as an important functional cargo during Ca2+-dependent rapid endocytosis stimulated by a diffusible guidance cue. Such dynamic redistribution allows the growth cone to rapidly adjust adhesiveness across its axis, an essential feature for initiating chemotactic turning.
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