TRPV4: A trigger of pathological RhoA activation in neurological disease.
TRPV4: A trigger of pathological RhoA activation in neurological disease.
复制标题
DOI：
10.1002/bies.202100288
复制
发表时间：
2022-06
期刊：
影响因子：
4
通讯作者：
McCray, Brett A.
中科院分区：
文献类型：
--
作者：
Bagnell, Anna M.;Sumner, Charlotte J.;McCray, Brett A.
瞬时受体电位香草酸4（TRPV 4）是TRP超家族的成员，是一种广泛表达的细胞表面定位的阳离子通道，可被各种环境刺激激活。重要的是，TRPV 4越来越多地参与细胞形态的调节。在这里，我们提出TRPV 4和细胞骨架重塑小GTdR RhoA一起构成了一个环境敏感的信号复合物，有助于神经损伤和疾病过程中的病理细胞细胞骨架改变。支持这一假设的是我们最近的工作证明TRPV 4与RhoA的直接物理和双向功能相互作用，这可以导致RhoA的激活和肌动蛋白细胞骨架的重组。此外，证据表明TRPV 4和/或RhoA参与了从中风到创伤性损伤的一系列急性神经损伤引发的病理反应。虽然由各种损伤引发，但TRPV 4-RhoA信号传导可能代表破坏轴突再生和血脑屏障完整性的共同途径。这些见解还表明，TRPV 4抑制可能代表了一种安全，可行和精确的治疗策略，用于限制一系列神经系统疾病中的病理性TRPV 4-RhoA激活。
Transient receptor potential vanilloid 4 (TRPV4), a member of the TRP superfamily, is a broadly expressed, cell surface-localized cation channel that is activated by a variety of environmental stimuli. Importantly, TRPV4 has been increasingly implicated in the regulation of cellular morphology. Here we propose that TRPV4 and the cytoskeletal remodeling small GTPase RhoA together constitute an environmentally sensitive signaling complex that contributes to pathological cell cytoskeletal alterations during neurological injury and disease. Supporting this hypothesis is our recent work demonstrating direct physical and bidirectional functional interactions of TRPV4 with RhoA, which can lead to activation of RhoA and reorganization of the actin cytoskeleton. Furthermore, a confluence of evidence implicates TRPV4 and/or RhoA in pathological responses triggered by a range of acute neurological insults ranging from stroke to traumatic injury. While initiated by a variety of insults, TRPV4–RhoA signaling may represent a common pathway that disrupts axonal regeneration and blood–brain barrier integrity. These insights also suggest that TRPV4 inhibition may represent a safe, feasible, and precise therapeutic strategy for limiting pathological TRPV4–RhoA activation in a range of neurological diseases.
登录
查看更多内容
影响因子：
4.3
作者：
Fujita Y;Yamashita T
通讯作者：
Yamashita T
影响因子：
7.7
作者：
Daneva Z;Ottolini M;Chen YL;Klimentova E;Kuppusamy M;Shah SA;Minshall RD;Seye CI;Laubach VE;Isakson BE;Sonkusare SK
通讯作者：
Sonkusare SK
影响因子：
7.4
作者：
Chen Y;Williams SH;McNulty AL;Hong JH;Lee SH;Rothfusz NE;Parekh PK;Moore C;Gereau RW 4th;Taylor AB;Wang F;Guilak F;Liedtke W
通讯作者：
Liedtke W
影响因子：
4.6
作者：
Glasgow, SM;Henkel, RM;Johnson, JE
通讯作者：
Johnson, JE
梓醇对 RhoA/ROCK-2 通路的抑制和紧密连接蛋白的上调可抑制脂多糖诱导的血脑屏障通透性破坏
DOI：
10.3390/molecules23092371
发表时间：
2018-09-17
期刊：
Molecules (Basel, Switzerland)
影响因子：
--
作者：
Feng S;Zou L;Wang H;He R;Liu K;Zhu H
通讯作者：
Zhu H