Critical role of collapsin response mediator protein-associated molecule CRAM for filopodia and growth cone development in neurons
Critical role of collapsin response mediator protein-associated molecule CRAM for filopodia and growth cone development in neurons
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DOI：
10.1091/mbc.e04-08-0679
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发表时间：
2005-01-01
影响因子：
3.3
通讯作者：
Yanagi, S
中科院分区：
文献类型：
--
作者：
Hotta, A;Inatome, R;Yanagi, S
溃缩蛋白反应介导蛋白（CRMPs）已被牵连在轴突导向的信号传导，包括信号蛋白。我们以前已经确定了这个基因家族的一个独特的成员，CRMP相关分子CRAM（CRMP-5），这是从其他四个CRMP的遗传学分歧。在这项研究中，我们研究了CRAM在发育神经元中的分布和功能。免疫组织化学分析显示CRAM在生长锥的丝状伪足中积累。使用细胞松弛素D的实验表明，CRAM的丝状伪足定位是独立的丝状肌动蛋白。CRAM在神经元细胞中的过表达显著促进丝状伪足的生长，并导致额外生长锥的形成，从而获得对semaphorin-3A刺激的抗性。最后，敲低CRAM通过使用RNA干扰阻断丝状伪足的形成，并揭示了异常形态的生长锥。我们建议，CRAM调节丝状伪足的动态和生长锥的发展，从而限制生长锥的反应，以排斥的指导线索。
Collapsin response mediator proteins (CRMPs) have been implicated in signaling of axonal guidance, including semaphorins. We have previously identified a unique member of this gene family, CRMP-associated molecule CRAM (CRMP-5), which is phylogenetically divergent from the other four CRMPs. In this study, we have examined the distribution and function of CRAM in developing neurons. Immunohistochemical analysis showed accumulation of CRAM in the filopodia of growth cones. Experiments using cytochalasin D indicated that filopodial localization of CRAM was independent of filamentous actin. Overexpression of CRAM in neuronal cells significantly promoted filopodial growth and led to the formation of supernumerary growth cones, which acquired resistance to semaphorin-3A stimulation. Finally, knockdown of CRAM by using RNA interference blocked filopodial formation and revealed an aberrant morphology of growth cones. We propose that CRAM regulates filopodial dynamics and growth cone development, thereby restricting the response of growth cone to repulsive guidance cues.