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通过KHSRP介导的轴性局部化Prenyl-Cdc42mRNA的衰变减缓了神经再生

M D Zdradzinski¹, Lauren S Vaughn¹, Samaneh Matoo¹

¹Department of Biological Sciences, University of South Carolina, Columbia, SC 20208 USA.

bioRxiv : the preprint server for biology

|February 20, 2025

概括

轴突的生长受到Prenyl-Cdc42mRNA的运输和翻译的调节,受生长信号的影响. KHSRP 蛋白质促进 Prenyl-Cdc42 mRNA 衰变,影响轴突再生.

科学领域:

神经科学是一个神经科学.
分子生物学分子生物学
细胞生物学细胞生物学

背景情况:

小型GTPase CDC42对于轴突生长至关重要,其介导的是actin聚合.
轴突的生长取决于特定mRNA的局部运输和翻译,例如Prenyl-Cdc42mRNA.

研究的目的:

为了研究轴突Prenyl-Cdc42mRNA运输和翻译在对增长调节刺激的反应中的调节.
确定控制 Prenyl-Cdc42 mRNA 稳定性和轴突中的传输的机制.
阐明KHSRP在调节Prenyl-Cdc42mRNA中的作用及其对轴突再生的影响.

主要方法:

在不同的生长条件下分析轴突mRNA传输和翻译.
研究KHSRP在mRNA衰变和结合中的作用.
使用Khsrp淘汰赛小鼠模型来评估轴突再生.

主要成果:

轴突Prenyl-Cdc42mRNA运输和翻译是由促进生长和抑制刺激调节的.
通过增加细胞内Ca2+和KHSRP的增长抑制导致Prenyl-Cdc42mRNA衰变.
KHSRP与Prenyl-Cdc42mRNA中的特定基因结合,其缺失导致轴突mRNA增加和增强再生.

结论:

轴突mRNA动态,特别是Prenyl-Cdc42,是轴突生长和再生的关键调节者.
KHSRP 作为 Prenyl-Cdc42 mRNA 的负调节剂,影响轴突再生.
向KHSRP或Prenyl-Cdc42mRNA可能是增强轴突修复的治疗策略.

关键词:

这是一种RNA结合蛋白.RNA局部化的RNA局部化在Rho GTPase中.神经再生的神经再生翻译控制的翻译控制

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