Latent process genes for cell differentiation are common decoders of neurite extension length
Latent process genes for cell differentiation are common decoders of neurite extension length
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DOI：
10.1242/jcs.097709
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发表时间：
2012-05-01
影响因子：
4
通讯作者：
Kuroda, Shinya
中科院分区：
文献类型：
--
作者：
Watanabe, Kanako;Akimoto, Yuki;Kuroda, Shinya
需要涉及信号转导和基因表达的潜在过程作为细胞功能的准备步骤。我们之前发现神经生长因子（NGF）诱导的细胞分化有一个潜在的过程，该过程依赖于ERK活性和基因表达，并且是随后的神经突延伸所必需的。潜在过程可以被视为将细胞外刺激信息解码为细胞功能的准备步骤；然而，这一过程的分子机制仍然未知。我们将 Metrnl、Dclk1 和 Serpinb1a 确定为在潜伏过程 (LP) 期间诱导的基因，具有不同的时间表达谱，并且是 PC12 细胞中随后的神经突延伸所必需的。 LP基因表现出对ERK活性持续时间的明显依赖性，并且它们也在PACAP和毛喉素诱导的细胞分化的潜伏过程中被诱导。无论神经营养因素如何，潜伏过程（0-12小时）期间LP基因的表达水平（而不是ERK的磷酸化水平）始终与随后的神经突延伸长度（12-24小时）相关。所有 LP 基因一起过表达，但不是每个基因单独过表达，增强了 NGF 诱导的神经突延伸。 LP基因产物表现出明显的空间定位。因此，无论神经营养因素如何，LP基因似乎都是神经突延伸长度的常见解码器，并且它们在潜在过程中可能以不同的时间和空间方式发挥作用。我们的研究结果提供了对潜在过程生理意义的分子洞察，作为解码未来表型变化信息的准备步骤。
A latent process involving signal transduction and gene expression is needed as a preparation step for cellular function. We previously found that nerve growth factor (NGF)-induced cell differentiation has a latent process, which is dependent on ERK activity and gene expression and required for subsequent neurite extension. A latent process can be considered as a preparation step that decodes extracellular stimulus information into cellular functions; however, molecular mechanisms of this process remain unknown. We identified Metrnl, Dclk1 and Serpinb1a as genes that are induced during the latent process (LP) with distinct temporal expression profiles and are required for subsequent neurite extension in PC12 cells. The LP genes showed distinct dependency on the duration of ERK activity, and they were also induced during the latent process of PACAP-and forskolin-induced cell differentiation. Regardless of neurotrophic factors, expression levels of the LP genes during the latent process (0-12 hours), but not phosphorylation levels of ERK, always correlated with subsequent neurite extension length (12-24 hours). Overexpression of all LP genes together, but not of each gene separately, enhanced NGF-induced neurite extension. The LP gene products showed distinct spatial localization. Thus, the LP genes appear to be the common decoders for neurite extension length regardless of neurotrophic factors, and they might function in distinct temporal and spatial manners during the latent process. Our findings provide molecular insight into the physiological meaning of the latent process as the preparation step for decoding information for future phenotypic change.