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CRMP-2 Is Involved in Kinesin-1-Dependent Transport of the Sra-1/WAVE1 Complex and Axon Formation

机译:CRMP-2参与Sra-1 / WAVE1复合物和轴突形成的依赖驱动蛋白1的运输。

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A neuron has two types of highly polarized cell processes, the single axon and multiple dendrites. One of the fundamental questions of neurobiology is how neurons acquire such specific and polarized morphologies. During neuronal development, various actin-binding proteins regulate dynamics of actin cytoskeleton in the growth cones of developing axons. The regulation of actin cytoskeleton in the growth cones is thought to be involved in axon outgrowth and axon-dendrite specification. However, it is largely unknown which actin-binding proteins are involved in axon-dendrite specification and how they are transported into the developing axons. We have previously reported that collapsin response mediator protein 2 (CRMP-2) plays a critical role in axon outgrowth and axon-dendrite specification (N. Inagaki, K. Chihara, N. Arimura, C. Menager, Y. Kawano, N. Matsuo, T. Nishimura, M. Amano, and K. Kaibuchi, Nat. Neurosci. >4:781-782, 2001). Here, we found that CRMP-2 interacted with the specifically Rac1-associated protein 1 (Sra-1)/WASP family verprolin-homologous protein 1 (WAVE1) complex, which is a regulator of actin cytoskeleton. The knockdown of Sra-1 and WAVE1 by RNA interference canceled CRMP-2-induced axon outgrowth and multiple-axon formation in cultured hippocampal neurons. We also found that CRMP-2 interacted with the light chain of kinesin-1 and linked kinesin-1 to the Sra-1/WAVE1 complex. The knockdown of CRMP-2 and kinesin-1 delocalized Sra-1 and WAVE1 from the growth cones of axons. These results suggest that CRMP-2 transports the Sra-1/WAVE1 complex to axons in a kinesin-1-dependent manner and thereby regulates axon outgrowth and formation.
机译:神经元具有两种类型的高度极化的细胞过程,单个轴突和多个树突。神经生物学的基本问题之一是神经元如何获得这种特定和极化的形态。在神经元发育过程中,各种肌动蛋白结合蛋白调节发育中的轴突生长锥中肌动蛋白细胞骨架的动力学。肌动蛋白细胞骨架在生长锥中的调节被认为与轴突的生长和轴突-树突的规格有关。然而,很大程度上未知哪些肌动蛋白结合蛋白参与轴突-树突规格以及如何将其转运到发育中的轴突中。我们以前曾报道过,胶原蛋白介导蛋白2(CRMP-2)在轴突生长和轴突-树突规格中起关键作用(N.Inagaki,K.Chihara,N.Arimura,C.Menager,Y.Kawano,N。 Matsuo,T.Nishimura,M.Amano,和K.Kaibuchi,Nat.Neurosci。> 4: 781-782,2001)。在这里,我们发现CRMP-2与Rac1相关蛋白1(Sra-1)/ WASP家庭Verprolin-同源蛋白1(WAVE1)复合物相互作用,后者是肌动蛋白细胞骨架的调节剂。 RNA干扰对Sra-1和WAVE1的抑制作用消除了培养的海马神经元中CRMP-2诱导的轴突生长和多轴突形成。我们还发现CRMP-2与kinesin-1的轻链相互作用并将kinesin-1链接到Sra-1 / WAVE1复合体。从轴突的生长锥中敲除CRMP-2和kinesin-1使Sra-1和WAVE1脱位。这些结果表明CRMP-2以驱动蛋白1依赖性的方式将Sra-1 / WAVE1复合物转运至轴突,从而调节轴突的生长和形成。

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