人类塑是一种新型的细胞骨pH传感器,在基本pH值下具有较低的F-actin捆绑能力
Lucas A Runyan1, Elena Kudryashova1, Richa Agrawal1
1Department of Chemistry and Biochemistry, The Ohio State University, Columbus, OH, USA, 43210.
bioRxiv : the preprint server for biology
|April 8, 2025
概括
塑蛋白 (PLS2和PLS3) 作为细胞内pH传感器,在性pH下降低了actin捆绑. 这种pH敏感度会影响细胞迁移和增殖,可能导致癌症的进展.
科学领域:
- 细胞生物学 细胞生物学
- 生物化学 生化学
- 分子生物学分子生物学
背景情况:
- 细胞内pH (pHi) 对于细胞平衡至关重要,调节细胞迁移和分裂等过程.
- 不调节的pH与包括癌症和代谢障碍在内的疾病有关.
- 已知很少有细胞骨蛋白质能够感知和响应pH值的变化.
研究的目的:
- 研究塑2 (PLS2) 和塑3 (PLS3) 作为细胞内pH传感器的作用.
- 为了确定pH值如何影响塑料的actin结合活性.
- 探索塑pH敏感性在细胞过程和疾病中的影响.
主要方法:
- 研究了生理学pH值波动对PLS2和PLS3.3对F-actin捆绑的影响.
- 分析了plastin的N端活性蛋白结合域 (ABD1) 与不同pH水平的活性蛋白的结合亲和力.
- 在不同的pH条件下观察了纤维细胞中异位表达PLS2的局部化.
- 在PLS2中识别和突变了一个关键的pH感应残留物 (His207),以评估其对捆绑活动的影响.
主要成果:
- 塑2 (PLS2) 和塑3 (PLS3) 在性pH下表现出减少的F-actin捆绑活性.
- 在更高的pH值下抑制PLS2捆绑是由于其N端的活性蛋白结合域 (ABD1) 的亲和力下降.
- 较高的细胞溶液pH导致PLS2与actin结构分离,而酸性pH则促进与焦点粘附和应力纤维的关联.
- 将His207转化为Lys或Tyr的突变改变了PLS2的pH灵敏度和作用素结合能力.
结论:
- 塑作为pH传感器起作用,调节actin细胞骨的动态,以应对pH的变化.
- 在性pH值下,塑的较弱的actin捆绑促进了actin分解和更快的动力学,这对细胞迁移和细胞运动至关重要.
- 塑的pH敏感性可能会导致性环境中的癌细胞扩散和转移.
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