Norman J C, Harrison P T, Davis W, Floto R A, Allen J M
Department of Medicine & Therapeutics, University of Glasgow, UK.
Immunology. 1998 May;94(1):48-55. doi: 10.1046/j.1365-2567.1998.00488.x.
The high-affinity receptor for immunoglobulin G (Fc gamma RI) plays a central role in the clearance of immune complexes by mediating their internalization and delivery to lysosomes. In monocytic U937 cells, receptor internalization is independent of tyrosine kinase activity. However, the tyrosine kinase inhibitor, genistein, prevents further progress of the receptor to lysosomes and traps it in a sub-plasma membrane early endosome. Similarly, Fc gamma RI expressed in COS cells is able to internalize immune complexes but is unable to translocate to lysosomes. This suggests that Fc gamma RI, whose cytoplasmic tail is devoid of known signalling motifs, must recruit tyrosine kinases via its gamma-chain to achieve lysosomal delivery. We show that a chimera of the extracellular domain of Fc gamma RI and the cytoplasmic tail of the gamma-chain is both internalized and efficiently trafficked to lysosomes. Our study suggests that a key function of the gamma-chain is recruitment of tyrosine kinases to initiate the intracellular signalling pathways required to target Fc gamma RI following immune complex aggregation to lysosomes and not to initiate endocytosis per se.
免疫球蛋白G高亲和力受体（FcγRI）通过介导免疫复合物的内化并将其递送至溶酶体，在免疫复合物的清除过程中发挥核心作用。在单核细胞U937细胞中，受体内化不依赖于酪氨酸激酶活性。然而，酪氨酸激酶抑制剂金雀异黄素可阻止受体进一步转运至溶酶体，并将其截留在质膜下早期内体中。同样，在COS细胞中表达的FcγRI能够内化免疫复合物，但无法转运至溶酶体。这表明，其胞质尾部缺乏已知信号基序的FcγRI必须通过其γ链招募酪氨酸激酶，以实现向溶酶体的递送。我们发现，FcγRI胞外结构域与γ链胞质尾部的嵌合体既能被内化，又能有效地转运至溶酶体。我们的研究表明，γ链的关键功能是招募酪氨酸激酶，以启动免疫复合物聚集后将FcγRI靶向溶酶体所需的细胞内信号通路，而不是启动内吞作用本身。
