Phosphorylation of CRMP2 (Collapsin Response Mediator Protein 2) Is Involved in Proper Dendritic Field Organization
Phosphorylation of CRMP2 (Collapsin Response Mediator Protein 2) Is Involved in Proper Dendritic Field Organization
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DOI：
10.1523/jneurosci.5563-11.2012
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发表时间：
2012-01
期刊：
影响因子：
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通讯作者：
N. Yamashita;T. Ohshima;F. Nakamura;Papachan Kolattukudy;J. Honnorat;K. Mikoshiba;Y. Goshima
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文献类型：
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作者：
N. Yamashita;T. Ohshima;F. Nakamura;Papachan Kolattukudy;J. Honnorat;K. Mikoshiba;Y. Goshima
溃缩蛋白反应介导蛋白（CRMP）是介导几种细胞外分子（如脑信号蛋白3A和神经营养因子）信号的细胞内蛋白。CRMP 1和CRMP 2在Ser 522处被Cdk 5磷酸化参与轴突引导和脊柱发育。在这里，我们发现Ser 522-磷酸化的CRMP 1和/或CRMP 2在培养的皮层神经元和P7皮层切片的树突中富集。为了确定CRMPs在树突发育中的生理作用，我们产生CRMP 2敲入突变小鼠（crmp 2ki/ki），其中522位的Ser残基被Ala取代。引人注目的是，双突变crmp 2ki/ki和crmp 1 −/−小鼠的皮质基底树突表现出严重的异常树突模式，我们将其定义为“卷曲表型”。这些发现表明，CRMP 1和CRMP 2的功能协同控制树突状投射，CRMP 2在Ser 522的磷酸化是必要的适当的树突状领域组织在体内。
Collapsin response mediator proteins (CRMPs) are intracellular proteins that mediate signals for several extracellular molecules, such as Semaphorin3A and neurotrophins. The phosphorylation of CRMP1 and CRMP2 by Cdk5 at Ser522 is involved in axonal guidance and spine development. Here, we found that the Ser522-phosphorylated CRMP1 and/or CRMP2 are enriched in the dendrites of cultured cortical neurons and P7 cortical section. To determine the physiological role of CRMPs in dendritic development, we generated CRMP2 knock-in mutant mice (crmp2ki/ki) in which the Ser residue at 522 was replaced with Ala. Strikingly, the cortical basal dendrites of double mutant crmp2ki/ki and crmp1−/− mice exhibited severe abnormal dendritic patterning, which we defined as “curling phenotype.” These findings demonstrate that the function of CRMP1 and CRMP2 synergistically control dendritic projection, and the phosphorylation of CRMP2 at Ser522 is essential for proper dendritic field organization in vivo.