Department of Molecular Pharmacology and Neurobiology, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan.
J Neurosci. 2012 Jan 25;32(4):1360-5. doi: 10.1523/JNEUROSCI.5563-11.2012.
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.
collapsin 反应介质蛋白 (CRMPs) 是一种细胞内蛋白，可介导多种细胞外分子（如 Semaphorin3A 和神经营养因子）的信号。Cdk5 对 CRMP1 和 CRMP2 的 Ser522 磷酸化参与了轴突导向和棘突发育。在这里，我们发现 Ser522 磷酸化的 CRMP1 和/或 CRMP2 在培养的皮质神经元和 P7 皮质切片的树突中富集。为了确定 CRMPs 在树突发育中的生理作用，我们生成了 Ser522 残基被 Ala 取代的 CRMP2 敲入突变小鼠（crmp2ki/ki）。引人注目的是，双突变 crmp2ki/ki 和 crmp1-/- 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 CRMP1 和 CRMP2 的功能协同控制树突投射，并且 CRMP2 的 Ser522 磷酸化对于体内适当的树突场组织至关重要。
