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Methods for Labeling Nonphagocytic Cells with MR Contrast Agents
Published in Michel M. J. Modo, Jeff W. M. Bulte, Molecular and Cellular MR Imaging, 2007
Joseph A. Frank, Stasia A. Anderson, Ali S. Arbab
Macropinocytosis is a method of endocytosis that allows for the uptake of larger particles from the extracellular space.16,17 It is an active process starting as an actin-driven membrane ruffle or extension from the plasma membrane. After encompassing the particles or ligands, the extension collapses into the plasma membrane, forming irregular-sized macropinosomes. There is recent evidence indicating that macropinocytosis is the mechanism by which arginine-containing protein transduction domains, including polyarginine, HIV transactivator transcription (Tat) proteins, peptides, polycationic macromolecular transfection agents, and cationic liposomes, get incorporated into the cell.17,27,28 Depending on its contents, the macropinosome may or may not fuse with deep lysosomes in the cells, and the contents would then undergo digestion by lysosomal enzymes and buffers.
Biotherapeutic effect of cell-penetrating peptides against microbial agents: a review
Published in Tissue Barriers, 2022
Idris Zubairu Sadiq, Aliyu Muhammad, Sanusi Bello Mada, Bashiru Ibrahim, Umar Aliyu Umar
Several clathrin-independent endocytosis routes mainly rely on caveolin-enclosed cholesterol-rich rafts to form invaginations of the caveolin membrane, whereas the clathrin-dependent endocytosis is composed of the protein clathrin, functioning as the main component of the endocytic vesicle coat, and is the most commonly recognized endocytic pathway67,70(Figure 2). Macropinocytosis is a type of endocytosis that eventually led to the internalization of fluids and membranes in large vacuoles through an endocytic actin-dependent pathway (Figure 2), thus creating a structure similar to a cup that closes to form a relatively large macropinosome.71 Macropinocytosis is an evolutionarily conserved type of endocytosis through nonselective uptake usually triggered in mammalian cells by growth factor-mediated stimulation of pathways PI3K and Ras.72 As Ras and PI3K become active, actin polymerization and membrane ruffling are facilitated by Rac1 and Rab5 small GTPases and PAK1 kinase, which influence the development and closure of macropinosomes.72–75 Compared to direct penetration, the endocytosis approach has the advantage of being faster because it uses energy and is more likely to move bulk materials in the shortest time possible.
Design, synthesis, and biological evaluation of 5-((4-(pyridin-3-yl)pyrimidin-2-yl)amino)-1H-Indole-2-Carbohydrazide derivatives: the methuosis inducer 12A as a Novel and selective anticancer agent
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2021
Jun Wu, Hongyu Hu, Mingtao Ao, Zhenzhen Cui, Xiaoping Zhou, Jingbo Qin, Yafei Guo, Jingwei Chen, Yuhua Xue, Meijuan Fang
Methuosis is characterised by the accumulation of cytoplasmic vacuoles derived from macropinosomes. It has been reported that protein synthesis is needed during macropinosome formation. Bafilomycin A1 (Baf-A1), a selective inhibitor of vacuolar-type H + ATPase (V-ATPase), can inhibit nascent macropinosome formation and restore the vacuoles to normal morphology by inhibiting acid influx in cells24. Cycloheximide (CHX) is a protein synthesis inhibitor that can disrupt the process of macropinosome formation24. Accordingly, HeLa cells were treated with 12A or in combination with Baf-A1 or CHX for 8 h, and the morphological changes were then imaged. As shown in Figure 4(C), both CHX and Baf-A1 dramatically blocked the formation of vacuoles, indicating that 12A was a methuosis inducer.
Versatility of cell-penetrating peptides for intracellular delivery of siRNA
Published in Drug Delivery, 2018
Tejinder Singh, Akula S. N. Murthy, Hye-Jin Yang, Jungkyun Im
The most understood pathway is the clathrin-mediated endocytosis which is constitutive to all mammalian cells. It is initiated and activated by binding of molecules to their corresponding transmembrane receptors and then the bound ligand-receptor complexes begin to form coated-pits mainly by clathrin, a representative coat-protein for vesicle formation(Sawant & Torchilin, 2010). The coated pits are invaginated with the support of actin, intersectin, cortactin, and epsin proteins. Subsequently, the GTPase dynamin is recruited to the neck of the coated pit which leads to the membrane fission. The clathrin-coated vesicles finally become endocytic. (Schafer, 2002; Sauvonnet et al., 2005; Messa et al., 2014). The caveolin-mediated pathway is a receptor-independent pathway that exhibits some similarities to the clathrin-mediated pathway because it also forms a flask-shaped pit, so-called caveolae (LeCher et al., 2017). The main protein involved in this process is caveolin which is an integral membrane protein that forms tight interactions with cholesterol present in the cell membrane. Thus, caveolin coat could be invaginated and pinched off from the cell membrane particularly in the cholesterol and sphingolipid-rich microdomains of the cell membrane (Roy & Wrana, 2005). This pathway is often referred to as detergent-resistant membranes (DRMs), detergent-insoluble glycolipid-enriched complexes (DIGs), or glycosphingolipid enriched membranes (GEMs) (Triantafilou et al., 2002). Macropinocytosis occurs constitutively in many cells to form a rather large vacuoles known as macropinosomes. In response to the cellular signaling, the process is initiated by an actin-mediated disruption of the plasma membrane (Lim & Gleeson, 2011). Ruffling and invagination of the cell membrane occurs and the resulting macropinosome will take up molecules from the extracellular fluid and finally deliver them into the cells (Bolhassani et al., 2017). Lastly, clathrin- and caveolae-independent endocytosis is distinct from the other endocytic pathways in that dynamin is not involved in the process. It has been proposed interleukin-2 receptor was internalized by generating a raft from the cell membrane. However, this process has not been studied much yet and is poorly understood (Figure 1).