Hager K M, Pierce M A, Moore D R, Tytler E M, Esko J D, Hajduk S L
Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, School of Medicine 35294.
J Cell Biol. 1994 Jul;126(1):155-67. doi: 10.1083/jcb.126.1.155.
The host range of Trypanosoma brucei brucei is restricted by the cytolytic effects of human serum high-density lipoprotein (HDL). The lytic activity is caused by a minor subclass of human serum HDL called trypanosome lytic factor (TLF). TLF binds in the flagellar pocket to specific TLF-binding sites. Internalization and localization of TLF to a population of endocytic vesicles, and ultimately large lysosome-like vesicles, precedes lysis of T. b. brucei. The membranes of these large vesicles are disrupted by the accumulation of TLF particles. Inhibitor studies with lysosomotropic amines have shown these large vesicles to be acidic in nature and that prevention of their rupture spares the cells from TLF-mediated lysis. Furthermore, leupeptin inhibition suggests that a thioprotease may be involved in the mechanism of TLF-mediated lysis of T. b. brucei. Based on these results, we propose a lytic mechanism involving cell surface binding, endocytosis and lysosomal targeting. This is followed by lysosomal disruption and subsequent autodigestion of the cell.
布氏布氏锥虫的宿主范围受到人血清高密度脂蛋白（HDL）的细胞溶解作用的限制。这种溶解活性是由人血清HDL的一个小亚类——锥虫溶解因子（TLF）引起的。TLF在鞭毛袋中与特定的TLF结合位点结合。在布氏布氏锥虫裂解之前，TLF会内化并定位到一群内吞小泡，最终定位到大型溶酶体样小泡。这些大型小泡的膜会因TLF颗粒的积累而破裂。用溶酶体促透胺进行的抑制剂研究表明，这些大型小泡本质上是酸性的，防止它们破裂可使细胞免受TLF介导的裂解。此外，亮抑蛋白酶肽抑制作用表明，一种硫醇蛋白酶可能参与了TLF介导的布氏布氏锥虫裂解机制。基于这些结果，我们提出了一种涉及细胞表面结合、内吞作用和溶酶体靶向的裂解机制。随后是溶酶体破裂以及细胞的自溶。
