Interfaculty Institute for Biochemistry, University of Tübingen, Hoppe-Seyler-Str, 4, D-72076 Tübingen, Germany.
BMC Neurosci. 2014 Jun 4;15:70. doi: 10.1186/1471-2202-15-70.
Localization of mRNAs encoding cytoskeletal or signaling proteins to neuronal processes is known to contribute to axon growth, synaptic differentiation and plasticity. In addition, a still increasing spectrum of mRNAs has been demonstrated to be localized under different conditions and developing stages thus reflecting a highly regulated mechanism and a role of mRNA localization in a broad range of cellular processes.
Applying fluorescence in-situ-hybridization with specific riboprobes on cultured neurons and nervous tissue sections, we investigated whether the mRNAs for two metabolic enzymes, namely glycogen synthase (GS) and glycogen phosphorylase (GP), the key enzymes of glycogen metabolism, may also be targeted to neuronal processes. If it were so, this might contribute to clarify the so far enigmatic role of neuronal glycogen. We found that the mRNAs for both enzymes are localized to axonal and dendritic processes in cultured lumbar spinal motoneurons, but not in cultured trigeminal neurons. In cultured cortical neurons which do not store glycogen but nevertheless express glycogen synthase, the GS mRNA is also subject to axonal and dendritic localization. In spinal motoneurons and trigeminal neurons in situ, however, the mRNAs could only be demonstrated in the neuronal somata but not in the nerves.
We could demonstrate that the mRNAs for major enzymes of neural energy metabolism can be localized to neuronal processes. The heterogeneous pattern of mRNA localization in different culture types and developmental stages stresses that mRNA localization is a versatile mechanism for the fine-tuning of cellular events. Our findings suggest that mRNA localization for enzymes of glycogen metabolism could allow adaptation to spatial and temporal energy demands in neuronal events like growth, repair and synaptic transmission.
已知编码细胞骨架或信号蛋白的 mRNAs 定位于神经元突起，有助于轴突生长、突触分化和可塑性。此外，越来越多的 mRNAs 已被证明在不同条件和发育阶段被定位，从而反映了高度调控的机制和 mRNA 定位在广泛的细胞过程中的作用。
我们应用荧光原位杂交技术，使用特定的核糖探针，在培养的神经元和神经组织切片上进行研究，以确定两种代谢酶，即糖原合酶（GS）和糖原磷酸化酶（GP）的 mRNAs 是否也可以靶向神经元突起。如果是这样，这可能有助于阐明神经元糖原迄今为止神秘的作用。我们发现，两种酶的 mRNAs 都定位于培养的腰脊髓运动神经元的轴突和树突突起中，但不在培养的三叉神经神经元中。在不储存糖原但仍表达糖原合酶的培养皮质神经元中，GS mRNA 也被定位于轴突和树突突起中。然而，在脊髓运动神经元和三叉神经神经元原位，只能在神经元胞体中检测到 mRNAs，而不能在神经中检测到。
我们能够证明神经能量代谢的主要酶的 mRNAs 可以定位于神经元突起。不同培养类型和发育阶段的 mRNA 定位的异质性模式强调了 mRNA 定位是精细调节细胞事件的多功能机制。我们的发现表明，糖原代谢酶的 mRNA 定位可以允许适应神经元事件（如生长、修复和突触传递）中的空间和时间能量需求。
