Howard Hughes Medical Institute, Tufts University School of Medicine, Boston, MA 02111, USA.
J Cell Biol. 2013 Jan 7;200(1):81-93. doi: 10.1083/jcb.201204090.
The process of phagocytosis in multicellular organisms is required for homeostasis, clearance of foreign particles, and establishment of long-term immunity, yet the molecular determinants of uptake are not well characterized. Cdc42, a Rho guanosine triphosphatase, is thought to orchestrate critical actin remodeling events needed for internalization. In this paper, we show that Cdc42 controls exocytic events during phagosome formation. Cdc42 inactivation led to a selective defect in large particle phagocytosis as well as a general decrease in the rate of membrane flow to the cell surface. Supporting the connection between Cdc42 and exocytic function, we found that the overproduction of a regulator of exocytosis, Rab11, rescued the large particle uptake defect in the absence of Cdc42. Additionally, we demonstrated a temporal interaction between Cdc42 and the exocyst complex during large particle uptake. Furthermore, disruption of exocyst function through Exo70 depletion led to a defect in large particle internalization, thereby establishing a functional role for the exocyst complex during phagocytosis.
在多细胞生物中，吞噬作用的过程对于维持体内平衡、清除外来颗粒和建立长期免疫是必需的，但吞噬作用的分子决定因素尚未得到很好的描述。CDC42 是一种 Rho 鸟苷三磷酸酶，被认为协调内化所需的关键肌动蛋白重塑事件。在本文中，我们表明 CDC42 控制着吞噬体形成过程中的胞吐事件。CDC42 的失活导致大颗粒吞噬作用的选择性缺陷以及细胞膜向细胞表面流动的总体速率下降。支持 CDC42 和胞吐功能之间的联系，我们发现胞吐作用调节剂 Rab11 的过度表达可以挽救 Cdc42 缺失时的大颗粒摄取缺陷。此外，我们在大颗粒摄取过程中证明了 CDC42 和外泌体复合物之间的时间相互作用。此外，通过 Exo70 耗竭破坏外泌体功能会导致大颗粒内化缺陷，从而在外泌体复合物在吞噬作用中建立了功能作用。
