Cell Biology Program, Sloan Kettering Institute for Cancer Research, New York, NY 10065, USA.
Cell Biology Program, Sloan Kettering Institute for Cancer Research, New York, NY 10065, USA; Louis V. Gerstner, Jr. Graduate School of Biomedical Sciences, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Cell Rep. 2019 Mar 19;26(12):3212-3220.e4. doi: 10.1016/j.celrep.2019.02.073.
Metazoan cell death mechanisms are diverse and include numerous non-apoptotic programs. One program called entosis involves the invasion of live cells into their neighbors and is known to occur in cancers. Here, we identify a developmental function for entosis: to clear the male-specific linker cell in C. elegans. The linker cell leads migration to shape the gonad and is removed to facilitate fusion of the gonad to the cloaca. We find that the linker cell is cleared in a manner involving cell-cell adhesions and cell-autonomous control of uptake through linker cell actin. Linker cell entosis generates a lobe structure that is deposited at the site of gonad-to-cloaca fusion and is removed during mating. Inhibition of lobe scission inhibits linker cell death, demonstrating that the linker cell invades its host while alive. Our findings demonstrate a developmental function for entosis: to eliminate a migrating cell and facilitate gonad-to-cloaca fusion, which is required for fertility.
后生动物细胞死亡的机制多种多样，包括许多非细胞凋亡程序。一种被称为“胞吞”的程序涉及活细胞侵入其邻近细胞，这种现象在癌症中很常见。在这里，我们发现了胞吞的一个发育功能：清除秀丽隐杆线虫中的雄性特异性连接细胞。连接细胞引导迁移以塑造生殖腺，并在生殖腺与直肠融合时被清除。我们发现，连接细胞的清除涉及细胞-细胞黏附和细胞自主控制摄取，通过连接细胞肌动蛋白进行。连接细胞的胞吞作用会产生一个叶状结构，该结构沉积在生殖腺与直肠融合的部位，并在交配过程中被清除。叶状结构分裂的抑制会抑制连接细胞的死亡，这表明连接细胞在其宿主还活着的时候就侵入了宿主。我们的研究结果证明了胞吞的一个发育功能：清除一个迁移的细胞，促进生殖腺与直肠的融合，这是生育所必需的。
