Moroni R F, De Biasi S, Colapietro P, Larizza L, Beghini A
Department of Biology and Genetics for Medical Sciences, Medical Faculty, University of Milan, Via Viotti 3/5, 20133 Milan, Italy.
Neuroscience. 2006 Nov 17;143(1):83-94. doi: 10.1016/j.neuroscience.2006.07.052. Epub 2006 Sep 14.
Protein kinases of the microtubule affinity-regulating kinase (MARK) family were originally discovered because of their ability to phosphorylate tau protein and related microtubule-associated proteins (MAPs), and their role in the establishment of cell polarity in different contexts. Recent papers have indicated that microtubule affinity-regulating kinase 4 (MARK4) is a gene that is finely regulated at transcriptional level and expressed in two spliced isoforms called MARK4L and MARK4S. We here describe the characterization of the mouse orthologue of the human MARK4 gene. Interestingly, MARK4S is predominantly expressed in the brain, whereas MARK4L shows lower transcript levels in this organ. Using MARK4 antibodies specific for each isoform, we found that both isoforms have an identical expression pattern in the mouse CNS, and are present in a number of neuronal populations. We also found that human microtubule affinity-regulating kinase 4S (hMARK4S), whose expression is not detectable in human neural progenitor cells (HNPCs) and NTera2 (NT2) cells, is up-regulated in both cell systems from the very early stages of neuronal differentiation. This indicates that neuronal commitment is marked by MARK4S up-regulation. In conclusion, this study provides the first direct evidence suggesting that MARK4 is a neuron-specific marker in the CNS, and the up-regulation of MARK4S during neuronal differentiation suggests that it plays a specialized role in neurons.
微管亲和力调节激酶（MARK）家族的蛋白激酶最初是因其能够磷酸化tau蛋白和相关微管相关蛋白（MAPs）以及在不同环境中建立细胞极性的作用而被发现的。最近的论文表明，微管亲和力调节激酶4（MARK4）是一个在转录水平受到精细调控的基因，以两种剪接异构体MARK4L和MARK4S的形式表达。我们在此描述了人类MARK4基因的小鼠同源物的特征。有趣的是，MARK4S主要在大脑中表达，而MARK4L在该器官中的转录水平较低。使用针对每种异构体的MARK4抗体，我们发现这两种异构体在小鼠中枢神经系统中具有相同的表达模式，并且存在于许多神经元群体中。我们还发现，人类微管亲和力调节激酶4S（hMARK4S）在人类神经祖细胞（HNPCs）和NTera2（NT2）细胞中无法检测到其表达，但在神经元分化的早期阶段，这两种细胞系统中其表达均上调。这表明神经元定向分化以MARK4S上调为标志。总之，本研究提供了首个直接证据，表明MARK4是中枢神经系统中的神经元特异性标志物，并且MARK4S在神经元分化过程中的上调表明它在神经元中发挥着特殊作用。
