Burkhardt J K, Hester S, Argon Y
Department of Microbiology and Immunology, Duke University Medical Center, Durham, NC 27710.
Proc Natl Acad Sci U S A. 1989 Sep;86(18):7128-32. doi: 10.1073/pnas.86.18.7128.
The granules of natural killer (NK) cells contain cytolysin and serine proteases, proteins that are expressed specifically in cytolytic cells and are released in response to target binding. We have used immunofluorescence and immunoelectron microscopy to localize these proteins with respect to the various morphological compartments of granules in a rat NK cell line. Both cytolysin and the proteases are limited to the core regions of the dense core granules. While these proteins are targeted to the same compartment, they differ markedly in their posttranslational processing. Cytolysin bears N-linked oligosaccharides that are converted to the complex type, while the major trypsin-like protease, granzyme A, bears only high-mannose-type oligosaccharides. The glycans of granzyme A, but not those of cytolysin, are modified with phosphomannose moieties. These results suggest that one possible mechanism for packaging proteins into NK granules is the mannose 6-phosphate-dependent lysosomal targeting system. However, the absence of the mannose 6-phosphate modification from cytolysin suggests the existence of yet another targeting system.
自然杀伤（NK）细胞的颗粒含有溶细胞素和丝氨酸蛋白酶，这些蛋白质在溶细胞细胞中特异性表达，并在与靶细胞结合后释放。我们利用免疫荧光和免疫电子显微镜，在大鼠NK细胞系中，相对于颗粒的各种形态学区室来定位这些蛋白质。溶细胞素和蛋白酶都局限于致密核心颗粒的核心区域。虽然这些蛋白质靶向同一区室，但它们在翻译后加工方面有显著差异。溶细胞素带有N-连接寡糖，这些寡糖会转化为复合型，而主要的类胰蛋白酶颗粒酶A仅带有高甘露糖型寡糖。颗粒酶A的聚糖，而非溶细胞素的聚糖，会被磷酸甘露糖部分修饰。这些结果表明，将蛋白质包装到NK颗粒中的一种可能机制是6-磷酸甘露糖依赖性溶酶体靶向系统。然而，溶细胞素缺乏6-磷酸甘露糖修饰表明还存在另一种靶向系统。
