Role of protein tyrosine phosphatases in organelle biogenesis

吞噬作用是细胞从其环境中内化大颗粒物质（衰老细胞，微生物）并将其隔离在吞噬体中的过程。这些新形成的吞噬体迅速成熟为吞噬溶酶体，其中内化的物质被降解。这个过程在广泛的细胞功能中发挥作用，从阿米巴的营养到哺乳动物的先天和适应性免疫。因此，吞噬溶酶体通过破坏微生物和允许将微生物抗原呈递给免疫系统在宿主防御中发挥核心作用。我们的研究项目旨在了解蛋白酪氨酸磷酸酶（PTPs）在吞噬溶酶体（一种模式细胞器）的生物发生和功能中的作用。吞噬溶酶体的生物发生需要多种信号分子的协调作用，包括蛋白激酶，其调节吞噬体和细胞骨架之间的相互作用，以及早期、晚期和再循环内吞隔室。酪氨酸（Tyr）磷酸化在吞噬体信号转导中的重要性，证明了这一发现，酪氨酸磷酸化位点在吞噬体蛋白质组中，相比于全球磷酸化蛋白质组。蛋白酪氨酸磷酸化的精确控制对于细胞内稳态是至关重要的，并且通过蛋白酪氨酸激酶和PTP的平衡作用来实现。** 对巨噬细胞PTP及其蛋白靶点在调节吞噬溶酶体生物发生和功能中的作用有越来越多的了解。我们希望我们的研究计划将有助于我们进一步了解Tyr磷酸化在这些过程中的作用。更好地了解PTPs及其参与吞噬溶酶体生物合成的靶点也可以更好地了解微生物的发病机制。

Phagocytosis is the process by which cells internalize large particulate materials (senescent cells, microbes) from their milieu and sequester them in phagosomes. These newly formed phagosomes rapidly mature into phagolysosomes where the internalized material is degraded. This process plays a role in a wide range of cell functions, ranging from nutrition in ameba to innate and adaptive immunity in mammals. Hence, phagolysosomes play a central role in host defence through the destruction of microbes and by allowing the presentation of microbial antigens to the immune system. Our research program is aimed at understanding the role(s) of protein tyrosine phosphatases (PTPs) in the biogenesis and function of phagolysosomes, a model organelle. Phagolysosome biogenesis requires the coordinated action of multiple signaling molecules, including protein kinases, which regulate the interactions between the phagosome and the cytoskeleton, as well as the early, late and recycling endocytic compartments. The importance of tyrosine (Tyr) phosphorylation in phagosome signaling was evidenced by the finding that Tyr phosphorylation sites are overrepresented in the phagosome proteome, as compared to global phosphoproteome. Precise control of protein tyrosine phosphorylation is crucial for cellular homeostasis, and is achieved by the balanced action of protein tyrosine kinases and PTPs. ******There is growing knowledge on the role of macrophage PTPs and their proteins targets in the regulation of phagolysosome biogenesis and function. We expect that our research program will contribute further to our understanding of the role of Tyr phosphorylation in these processes. Better knowledge of the PTPs and their targets involved in phagolysosome biogenesis may also provide a better understanding of microbial pathogenesis.