Yu Xiaomeng, Odera Sampeter, Chuang Chin-Hua, Lu Nan, Zhou Zheng
Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
Dev Cell. 2006 Jun;10(6):743-57. doi: 10.1016/j.devcel.2006.04.007.
Dynamins are large GTPases that act in multiple vesicular trafficking events. We identified 14 loss-of-function alleles of the C. elegans dynamin gene, dyn-1, that are defective in the removal of apoptotic cells. dyn-1 functions in engulfing cells to control the internalization and degradation of apoptotic cells. dyn-1 acts in the genetic pathway composed of ced-7 (ABC transporter), ced-1 (phagocytic receptor), and ced-6 (CED-1's adaptor). DYN-1 transiently accumulates to the surface of pseudopods in a manner dependent on ced-1, ced-6, and ced-7, but not on ced-5, ced-10, or ced-12. Abnormal vesicle structures accumulate in engulfing cells upon dyn-1 inactivation. dyn-1 and ced-1 mutations block the recruitment of intracellular vesicles to pseudopods and phagosomes. We propose that DYN-1 mediates the signaling of the CED-1 pathway by organizing an intracellular vesicle pool and promoting vesicle delivery to phagocytic cups and phagosomes to support pseudopod extension and apoptotic cell degradation.
发动蛋白是一类大型GTP酶，在多种囊泡运输事件中发挥作用。我们鉴定出了秀丽隐杆线虫发动蛋白基因dyn-1的14个功能丧失等位基因，这些基因在凋亡细胞清除方面存在缺陷。dyn-1在吞噬细胞中发挥作用，以控制凋亡细胞的内化和降解。dyn-1作用于由ced-7（ABC转运蛋白）、ced-1（吞噬受体）和ced-6（CED-1的衔接蛋白）组成的遗传途径。DYN-1以依赖于ced-1、ced-6和ced-7，但不依赖于ced-5、ced-10或ced-12的方式短暂积累到伪足表面。dyn-1失活后，异常的囊泡结构在吞噬细胞中积累。dyn-1和ced-1突变会阻止细胞内囊泡募集到伪足和吞噬体。我们提出，DYN-1通过组织细胞内囊泡池并促进囊泡递送至吞噬杯和吞噬体，以支持伪足延伸和凋亡细胞降解，从而介导CED-1途径的信号传导。
