Xiong Weipeng, Chen Yongmei, Wang Huizhen, Wang Haikun, Wu Hui, Lu Qingxian, Han Daishu
Department of Cell Biology, School of Basic Medicine, Peking Union Medical College, Institute of Chinese Basic Medical Sciences, Chinese Academy of Medical Sciences, 5 Dong Dan San Tiao, Beijing 100005, People's Republic of China.
Reproduction. 2008 Jan;135(1):77-87. doi: 10.1530/REP-07-0287.
The apoptotic spermatogenic cells and residual bodies are phagocytosed and degraded by Sertoli cells during spermatogenesis. The mechanisms of this process are largely unknown. Here, we demonstrate that Gas6 and its receptors, the Tyro 3 subfamily of receptor tyrosine kinases (RTKs; Tyro 3, Axl, and Mer), regulate the phagocytic function of Sertoli cells. The phagocytic ability of Sertoli cells increased by five times in the presence of Gas6 in serum-free medium when compared with controls. The Sertoli cells lacking Mer showed a 35% reduction in phagocytosis of apoptotic spermatogenic cells when compared with wild-type (WT) controls, whereas the Sertoli cells lacking Tyro 3 or Axl exhibited phagocytic activity comparable with the controls. Notably, the Sertoli cells lacking all three members of the Tyro 3 RTK subfamily showed a dramatic decrease in phagocytic ability of 7.6-fold when compared with WT Sertoli cells. The deficiency in phagocytosis by the triple-mutant Sertoli cells was due to the deficit in binding of the Sertoli cells to apoptotic germ cells. These findings suggest that Mer is responsible for triggering phagocytosis of apoptotic spermatogenic cells by Sertoli cells and that Tyro 3, Axl, and Mer participate in recognizing and binding apoptotic germ cells by Sertoli cells in a redundant manner. Gas6 is a functional ligand of the Tyro 3 RTK subfamily in mediating phagocytic ability of Sertoli cells.
在精子发生过程中，凋亡的生精细胞和残余体被支持细胞吞噬并降解。这一过程的机制在很大程度上尚不清楚。在此，我们证明Gas6及其受体，即受体酪氨酸激酶（RTK）的Tyro 3亚家族（Tyro 3、Axl和Mer），调节支持细胞的吞噬功能。与对照组相比，在无血清培养基中存在Gas6时，支持细胞的吞噬能力提高了五倍。与野生型（WT）对照组相比，缺乏Mer的支持细胞对凋亡生精细胞的吞噬作用降低了35%，而缺乏Tyro 3或Axl的支持细胞表现出与对照组相当的吞噬活性。值得注意的是，与WT支持细胞相比，缺乏Tyro 3 RTK亚家族所有三个成员的支持细胞的吞噬能力急剧下降了7.6倍。三突变支持细胞吞噬作用的缺陷是由于支持细胞与凋亡生殖细胞结合的不足。这些发现表明，Mer负责触发支持细胞对凋亡生精细胞的吞噬作用，并且Tyro 3、Axl和Mer以冗余方式参与支持细胞识别和结合凋亡生殖细胞。Gas6是Tyro 3 RTK亚家族在介导支持细胞吞噬能力方面的功能性配体。
