Department of Biochemistry, School of Medicine, Dongguk University, Gyeongju 780-714, Republic of Korea.
Biochem Biophys Res Commun. 2010 Jul 30;398(3):467-72. doi: 10.1016/j.bbrc.2010.06.101. Epub 2010 Jun 27.
The clearance of apoptotic cells is critical during cellular homeostasis as well as inflammation resolution. Recently, we found that stabilin-1 is a phagocytic receptor that is involved in the clearance of apoptotic cells. However, the downstream signaling pathway of stabilin-1-mediated phagocytosis remains to be investigated. Here we identify that GULP is able to specifically interact with the NPxF/Y motif of stabilin-1 cytoplasmic region. The PTB domain of GULP is necessary for interaction with stabilin-1. GULP is enriched around PS-coated beads for phagocytosis and co-localized with stabilin-1. Downregulation of endogenous GULP expression decreased stabilin-1-mediated phagocytosis. Thus, these results indicate that GULP functions as an adaptor protein for stabilin-1-mediated phagocytosis.
细胞凋亡清除对于细胞内稳态和炎症消退至关重要。最近，我们发现稳定素-1是一种吞噬受体，参与细胞凋亡清除。然而，稳定素-1介导的吞噬作用的下游信号通路仍有待研究。在这里，我们发现 GULP 能够特异性地与稳定素-1胞质区的 NPxF/Y 基序相互作用。GULP 的 PTB 结构域对于与稳定素-1相互作用是必需的。GULP 在吞噬作用中富含 PS 包被珠，并且与稳定素-1共定位。内源性 GULP 表达下调降低了稳定素-1介导的吞噬作用。因此，这些结果表明 GULP 作为稳定素-1介导的吞噬作用的衔接蛋白发挥作用。
