Paglini G, Pigino G, Kunda P, Morfini G, Maccioni R, Quiroga S, Ferreira A, Cáceres A
Instituto Mercedes y Martín Ferreyra, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), 5000 Cordoba, Argentina.
J Neurosci. 1998 Dec 1;18(23):9858-69. doi: 10.1523/JNEUROSCI.18-23-09858.1998.
Cultures of cerebellar macroneurons were used to study the pattern of expression, subcellular localization, and function of the neuronal cdk5 activator p35 during laminin-enhanced axonal growth. The results obtained indicate that laminin, an extracellular matrix molecule capable of selectively stimulating axonal extension and promoting MAP1B phosphorylation at a proline-directed protein kinase epitope, selectively stimulates p35 expression, increases its association with the subcortical cytoskeleton, and accelerates its redistribution to the axonal growth cones. Besides, suppression of p35, but not of a highly related isoform designated as p39, by antisense oligonucleotide treatment selectively reduces cdk5 activity, laminin-enhanced axonal elongation, and MAP1b phosphorylation. Taken collectively, the present results suggest that cdk5/p35 may serve as an important regulatory linker between environmental signals (e.g., laminin) and constituents of the intracellular machinery (e.g., MAP1B) involved in axonal elongation.
利用小脑大神经元培养物来研究层粘连蛋白增强轴突生长过程中神经元周期蛋白依赖性激酶5（cdk5）激活剂p35的表达模式、亚细胞定位及功能。所获结果表明，层粘连蛋白作为一种能够选择性刺激轴突延伸并在脯氨酸定向蛋白激酶表位促进微管相关蛋白1B（MAP1B）磷酸化的细胞外基质分子，可选择性刺激p35表达，增加其与皮质下细胞骨架的结合，并加速其重新分布至轴突生长锥。此外，通过反义寡核苷酸处理抑制p35而非高度相关的异构体p39，可选择性降低cdk5活性、层粘连蛋白增强的轴突伸长及MAP1b磷酸化。总体而言，目前结果提示，cdk5/p35可能作为环境信号（如层粘连蛋白）与参与轴突伸长的细胞内机制成分（如MAP1B）之间的重要调控连接物。
