Coordinated balance of Rac1 and RhoA plays key roles in determining phagocytic appetite.
Coordinated balance of Rac1 and RhoA plays key roles in determining phagocytic appetite.
复制标题
DOI：
10.1371/journal.pone.0174603
复制
发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Kim IS
中科院分区：
文献类型：
--
作者：
Kim SY;Kim S;Bae DJ;Park SY;Lee GY;Park GM;Kim IS
吞噬细胞清除不需要的或受损的细胞是通过一个被称为efferocytosis的精细调节的清洁过程来实现的。为了描述吞噬细胞控制凋亡细胞摄取的机制，我们研究了吞噬杯中的RhoA和Rac1如何协调吞噬细胞对被吞噬细胞的食欲。我们使用FRET生物传感器可视化rho家族gtpase的时空动态，发现已知在吞噬过程中下调的RhoA在吞噬杯中瞬间上调。相反，Rac1在吞噬过程中上调，然后在吞噬体成熟之前下调。此外，RhoA的动态活动受到干扰，导致不受控制的吞噬，如快速和不识别进食。我们的研究结果表明，RhoA GTPase的时间活性改变了摄入前吞噬杯中的Rac1/RhoA平衡，并且这在协调efferocytosis中起着独特的作用，RhoA调节吞噬速率以确保吞噬细胞吞噬适量的正确物质。
The removal of unwanted or damaged cells by phagocytes is achieved via a finely regulated cleaning process called efferocytosis. To characterize the mechanisms through which phagocytes control the intake of apoptotic cells, we investigated how the phagocyte’s appetite for engulfed cells may be coordinated by RhoA and Rac1 in the phagocytic cup. We used FRET biosensors to visualize the spatiotemporal dynamics of Rho-family GTPases, and found that RhoA, which is known to be downregulated during phagocytosis, was transiently upregulated at the phagocytic cup immediately prior to ingestion. Conversely, Rac1 was upregulated during the engulfment process and then downregulated prior to phagosomal maturation. Moreover, disturbance of the dynamic activities of RhoA led to uncontrolled engulfment, such as fast and undiscerning eating. Our results reveal that the temporal activity of RhoA GTPase alters the Rac1/RhoA balance at the phagocytic cup prior to ingestion, and that this plays a distinct role in orchestrating efferocytosis, with RhoA modulating the rate of engulfment to ensure that the phagocyte engulfs an appropriate amount of the correct material.