CRMP-2 regulates polarized Numb-mediated endocytosis for axon growth
CRMP-2 regulates polarized Numb-mediated endocytosis for axon growth
复制标题
DOI：
10.1038/ncb1039
复制
发表时间：
2003-09-01
影响因子：
21.3
通讯作者：
Kaibuchi, K
中科院分区：
文献类型：
--
作者：
Nishimura, T;Fukata, Y;Kaibuchi, K
神经发育期间轴突的生长高度依赖于细胞骨架的重组和极化膜的运输。在此之前，我们已经证明，崩溃素反应介体蛋白-2(CRMP-2)对于决定培养的海马神经元的轴突/树突命运和轴突生长至关重要，可能是通过与微管蛋白异二聚体相互作用，促进微管组装。在这里，我们确定Numb是一个CRMP-2相互作用蛋白。Numb已被证明与α-Adaptin相互作用，并参与内吞作用。我们发现Numb与L1相关，L1是一种神经细胞黏附分子，在生长锥体内被内吞和循环，CRMP-2和Numb在生长锥共定位。此外，显性负性CRMP-2突变体的表达或用小干扰(Si)RNA敲除CRMP-2信息会抑制L1在轴突生长锥的内吞作用，并抑制轴突生长。这些结果表明，除了调节微管组装，CRMP-2还参与L1等蛋白质的极化Numb介导的内吞作用。
Axon growth during neural development is highly dependent on both cytoskeletal re-organization and polarized membrane trafficking. Previously, we demonstrated that collapsin response mediator protein-2 (CRMP-2) is critical for specifying axon/dendrite fate and axon growth in cultured hippocampal neurons, possibly by interacting with tubulin heterodimers and promoting microtubule assembly. Here, we identify Numb as a CRMP-2-interacting protein. Numb has been shown to interact with alpha-adaptin and to be involved in endocytosis. We found that Numb was associated with L1, a neuronal cell adhesion molecule that is endocytosed and recycled at the growth cone, where CRMP-2 and Numb were colocalized. Furthermore, expression of dominant-negative CRMP-2 mutants or knockdown of CRMP-2 message with small-interfering (si) RNA inhibited endocytosis of L1 at axonal growth cones and suppressed axon growth. These results suggest that in addition to regulating microtubule assembly, CRMP-2 is involved in polarized Numb-mediated endocytosis of proteins such as L1.