WNK 激酶是内皮细胞中的血管活性化物传感器
Tessa A C Garrud1, Briar Bell1,2, Alejandro Mata-Daboin1
1Department of Physiology, University of Tennessee Health Science Center, Memphis, TN 38163.
概括
内皮细胞通过TMEM16A通道使用化物 (Cl-) 信号来激活WNK激酶. 这一途径调节TRPV4通道,增加,并引起血管扩张以控制动脉收缩性.
科学领域:
- 生理学 生理学 生理学
- 分子生物学分子生物学
- 血管生物学 血管生物学
背景情况:
- 内皮细胞 (ECs) 调节血流和血压.
- 细胞内化物 (Cl-) 和无-lysine (WNK) 激酶存在于ECs.
- 它们在EC功能和动脉收缩性中的作用尚未完全理解.
研究的目的:
- 调查ECs中的细胞内Cl-信号是否调节动脉收缩性.
- 检查参与这个过程的信号机制,包括WNK激酶.
主要方法:
- 使用双光子显微镜和细胞特异性诱导性淘汰小鼠.
- 高速光谱显微镜捕获了四维的细胞内Ca2+信号.
- 测试测量了化物度和WNK激酶活性.
主要成果:
- 乙胆通过TMEM16A通道激活诱导了EC细胞内细胞内Cl-度 ([Cl-]i) 的快速降低.
- TMEM16A的激活导致了WNK激酶的激活,酸化SPAK和OSR1.1.
- OSR1增强了TRPV4电流,增加了细胞内Ca2+并导致血管扩张.
结论:
- TMEM16A通道的激活减少了[Cl-]i,激活了ECs中的WNK激酶.
- 基酶酸化OSR1,刺激TRPV4通道,导致血管扩张.
- 这条涉及TMEM16A,WNK激酶和TRPV4的途径调节EC功能和动脉收缩性.
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