Pigino G, Paglini G, Ulloa L, Avila J, Cáceres A
Instituto Investigación Médica Mercedes y Martín Ferreyra, Córdoba, Argentina.
J Cell Sci. 1997 Jan;110 ( Pt 2):257-70. doi: 10.1242/jcs.110.2.257.
Cultures of cerebellar macroneurons were used to study the expression, activity, subcellular localization, and function of cdk5 during neuronal morphogenesis. The results obtained indicate that in non-polarized neurons cdk5 is restricted to the cell body but as soon as polarity is established it becomes highly concentrated at the distal tip of growing axons where it associates with microtubules and the subcortical cytoskeleton. In addition, we show that laminin, an extracellular matrix molecule capable of stimulating axonal extension and promoting MAP1b phosphorylation (DiTella et al., 1996), accelerates the redistribution of cdk5 to the axonal tip and dramatically increases its activity. Finally, our results indicate that cdk5 suppression by antisense oligonucleotide treatment selectively reduces axonal elongation and decreases the phosphorylation status of MAP1b, as well as its binding to microtubules. Taken collectively, our observations suggest that cdk5 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 formation.
利用小脑大神经元培养物来研究细胞周期蛋白依赖性激酶5（cdk5）在神经元形态发生过程中的表达、活性、亚细胞定位及功能。所获结果表明，在非极化神经元中，cdk5局限于细胞体，但一旦建立极性，它就会高度集中在生长轴突的远端，在那里它与微管和皮质下细胞骨架相关联。此外，我们发现层粘连蛋白，一种能够刺激轴突延伸并促进微管相关蛋白1b（MAP1b）磷酸化的细胞外基质分子（迪特拉等人，1996年），加速了cdk5向轴突末端的重新分布，并显著增加其活性。最后，我们的结果表明，通过反义寡核苷酸处理抑制cdk5会选择性地减少轴突伸长，并降低MAP1b的磷酸化状态及其与微管的结合。总体而言，我们的观察结果表明，cdk5可能作为环境信号（如层粘连蛋白）与参与轴突形成的细胞内机制成分（如MAP1b）之间的重要调节连接物。
