Collins Richard F, Schreiber Alan D, Grinstein Sergio, Trimble William S
Program in Cell Biology, Research Institute, The Hospital for Sick Children, and Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada.
J Immunol. 2002 Sep 15;169(6):3250-6. doi: 10.4049/jimmunol.169.6.3250.
The phagosome is a dynamic organelle that undergoes progressive changes to acquire the machinery required to kill and degrade internalized foreign particles. This maturation process involves sequential interaction of newly formed phagosomes with several components of the endocytic pathway. The proteins that mediate the ordered fusion of endosomes and lysosomes with the phagosome are not known. In this study, we investigated the possible role of syntaxins present in the endo/lysosomal pathway in directing phagosomal maturation. We show that in phagocytic cells syntaxin 13 is localized to the recycling endosome compartment, while syntaxin 7 is found in late endosomes/lysosomes. Both proteins are recruited to the phagosome, but syntaxin 13 is acquired earlier and rapidly recycles off the phagosome, while syntaxin 7 is recruited later and continues to accumulate throughout the maturation process. Overexpression of truncated (cytosolic) forms of syntaxin 13 or 7 had no effect on phagocytosis, but exerted an inhibitory effect on phagosomal maturation. These results indicate that syntaxins 13 and 7 are both required for interaction of endosomes and/or lysosomes with the phagosome, but play distinct roles in the maturation process.
吞噬体是一种动态细胞器,会经历渐进性变化以获得杀死和降解内化异物所需的机制。这种成熟过程涉及新形成的吞噬体与内吞途径的几个组分的顺序相互作用。介导内体和溶酶体与吞噬体有序融合的蛋白质尚不清楚。在本研究中,我们研究了存在于内体/溶酶体途径中的 syntaxin 在指导吞噬体成熟中的可能作用。我们发现,在吞噬细胞中,syntaxin 13 定位于再循环内体区室,而 syntaxin 7 存在于晚期内体/溶酶体中。这两种蛋白质都被募集到吞噬体,但 syntaxin 13 更早被募集并迅速从吞噬体上循环,而 syntaxin 7 较晚被募集并在整个成熟过程中持续积累。截断形式(胞质形式)的 syntaxin 13 或 7 的过表达对吞噬作用没有影响,但对吞噬体成熟有抑制作用。这些结果表明,syntaxin 13 和 7 都是内体和/或溶酶体与吞噬体相互作用所必需的,但在成熟过程中发挥不同的作用。