Institute for Molecular Bioscience (IMB), The University of Queensland, Brisbane, QLD 4072, Australia.
Institute for Molecular Bioscience (IMB), The University of Queensland, Brisbane, QLD 4072, Australia.
Curr Opin Cell Biol. 2020 Aug;65:131-140. doi: 10.1016/j.ceb.2020.06.005. Epub 2020 Jul 31.
Macropinocytosis is increasingly recognized for its versatile adaptations and functions as a highly conserved, ubiquitous pathway for the bulk uptake of fluid, particulate cargo, and membranes. Innate immune cells and transformed cancer cells share the capacity for both constitutive and induced macropinocytosis, which is used for immune surveillance, ingestion of pathogens, immune response shaping, and enhancement of scavenging for nutrients as fuel for cell survival and proliferation. Immunology and cancer biology are leading a resurgence of interest in defining the molecular and physiological regulation of macropinocytosis, partly in pursuit of ways to control macropinocytic uptake in disease settings. New approaches, including high-resolution live imaging, screening of cell surface molecular inventories, biophysics, and exploration of cell microenvironments, have converged to provide new insights into macropinosome induction, formation, and maturation. Recent studies reveal mechanisms for fluid control in and by macrophage macropinosomes that impinge on membrane trafficking and cell migration. EGFR, PTEN, V-ATPase, syndecan 1, and galectin-3 have roles variably in the metabolic regulation of Ras or PI3K signaling for Rac1-mediated macropinocytosis in cancer. These molecular pathways and mechanisms contribute to the impressive adaptability of macropinocytosis in many cells and tissues and in disease.
巨胞饮作用越来越被认为是一种多功能的适应和功能，作为一种高度保守的、普遍存在的途径，用于大量摄取流体、颗粒货物和膜。先天免疫细胞和转化的癌细胞都具有组成型和诱导型巨胞饮作用的能力，这用于免疫监视、病原体摄取、免疫反应的塑造以及增强对营养物质的清除，以作为细胞存活和增殖的燃料。免疫学和癌症生物学正在重新引起人们对巨胞饮作用的分子和生理调节的兴趣，部分原因是为了寻找在疾病环境中控制巨胞饮作用的方法。新的方法，包括高分辨率活细胞成像、细胞表面分子目录筛选、生物物理学以及细胞微环境的探索，已经汇聚在一起，为巨胞饮诱导、形成和成熟提供了新的见解。最近的研究揭示了巨噬细胞巨胞饮作用中的流体控制机制，这些机制影响了膜运输和细胞迁移。EGFR、PTEN、V-ATPase、 syndecan 1 和半乳糖凝集素-3 在不同程度上参与了 Ras 或 PI3K 信号通路的代谢调节，以介导癌症中的 Rac1 介导的巨胞饮作用。这些分子途径和机制有助于巨胞饮作用在许多细胞和组织以及疾病中的惊人的适应性。
