CRB2 枯竭会诱导 YAP 信号,并破坏受体细胞中的机械感知
Yingyu Sun1, Nils M Kronenberg1, Sidharth K Sethi2
1Humboldt Centre for Nano- and Biophotonics, Department of Chemistry, University of Cologne, Cologne, Germany.
bioRxiv : the preprint server for biology
|November 1, 2024
概括
CRB2基因突变导致脏疾病 (FSGS). 缺少CRB2会损害细胞机械传导,破坏YAP信号传递并影响细胞收缩性,为FSGS的病原性提供了新的见解.
科学领域:
- 腎臟病學 (nephrology) 是一種醫學專業.
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 焦点细分细胞凝聚硬化 (FSGS) 是一种病,其特征是受细胞损伤.
- CRB2基因的突变与早期发病的类固醇耐药性瘤综合征 (SRNS) /FSGS有关.
- 一个特定的东亚亲属 (DUK40595) 呈现SRNS/FSGS由于复合异体CRB2突变.
研究的目的:
- 为了研究CRB2缺乏在podocytes的致病性影响.
- 阐明CRB2在细胞机械传导和YAP信号传导中的作用.
主要方法:
- 在受体细胞中,CRB2被淘汰.
- 对YAP活动和基因表达的分析.
- 评估焦点粘附和F-actin密度.
- 弹性共振干扰应力显微镜 (ERISM) 用于测量细胞收缩性.
- 使用YAP抑制剂的治疗 (K-975,脊).
主要成果:
- 抑制CRB2增加了YAP活性和细胞中的基因表达.
- 缺少CRB2导致受体细胞收缩性增强和焦点粘附/F-actin密度增加.
- 在CRB2淘汰细胞中观察到受损的机械感知,特别是在基质刚度低的情况下.
- 增强的细胞收缩性并未完全被YAP抑制逆转,这表明多个下游途径.
结论:
- 缺少CRB2会影响细胞机械传导.
- 对YAP信号的干扰与CRB2相关的 podocyte 功能障碍有关.
- 这些发现为FSGS由CRB2突变引起的机制提供了新的见解.
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