![]() Cell fragments thus may play important roles in physiology and pathology through active participation in homeostasis, phagocytosis, and cell-cell communication ( Mannel and Grau, 1997 Bang and Thum, 2012 Arnold and Kahwash, 2014). Cells can also shed smaller fragments like exosomes. Migration of fragments from glioma cells correlate with malignancy ( Yount et al., 2007). Cell fragments from white blood cells (also called cytokineplasts or cytoplasts) retain chemotactic, phagocytic, and microbicidal function in vitro and in vivo ( Malawista et al., 1989 Malawista et al., 1992 Malawista et al., 2006). Recent experiments provide convincing evidence demonstrating that platelets are mobile, able to migrate over a surface, and transmigrate through a basement membrane and endothelium toward a chemoattractant source ( Kraemer et al., 2010 Schmidt et al., 2011). Blood platelets play an essential role in coagulation, and are specialized type of cells which were believed to be static and immobile once they adhere to a matrix ( Valone et al., 1974). However, cell fragments devoid of the nuclear and major organelles, in which signaling is likely very different from that of the mother cells, are also able to manifest robust motility and directional migration. ![]() Signaling networks govern cell migration ( Ridley et al., 2003). Our results suggest that cAMP and cGMP are essential for galvanotaxis of cell fragments, in contrast to the signaling mechanisms in parental cells. Inhibition of cathode signaling with PI3K inhibitor LY294002 also prevented the effects of cAMP or cGMP agonists. Both perturbations confirmed that the inhibitory effect was mediated by cAMP or cGMP signaling. Blocking cAMP and cGMP downstream signaling by inhibition of PKA and PKG also recovered fragment galvanotaxis. The inhibition effects were prevented by pre-incubating with cAMP and cGMP antagonists. cAMP or cGMP agonists completely abolished directional migration of fragments, but had no effect on parental cells. Here we used fish keratocyte fragments and demonstrated striking differences in signal transduction in migration of cell fragments and parental cells in a weak electric field. Signaling mechanisms underlying migration of cell fragments are poorly understood. Fragments from white blood cells display chemotaxis, phagocytosis, and bactericidal functions. The researchers are continuing to study this process in detail to find out more about the precise mechanism and piece together a detailed account of the fate of proteins, from dead cells to dendritic cells.Cell fragments devoid of the nucleus and major organelles are found in physiology and pathology, for example platelets derived from megakaryocytes, and cell fragments from white blood cells and glioma cells. “A better understanding of this process, which is fundamental to our immune system, could lead to new ways to exploit our body’s natural defences against infection and cancer.” We’ve been working on this for many years so it’s exciting to finally have evidence of a specific receptor which signals for phagosomes to burst. The researchers found that key to this mechanism is a receptor called DNGR-1.Ĭaetano Reis e Sousa, author and group leader of the Immunobiology Laboratory at the Crick says: “For decades there has been a question over how proteins within phagosomes escape in order to be chopped up and presented at the dendritic cell surface. There, the proteins get chopped into small fragments that travel to the dendritic cell surface and are presented to the T-cells. University of Cambridge, Department of Medicine, Addenbrooke’s Hospitalīy studying this process in mouse immune cells, the researchers found that in order to present the dead cell proteins to T-cells, invoking a response, the phagosome bursts, setting the proteins free within the inside of the dendritic cell.Division of Protein and Nucleic Acid Chemistry, at MRC Laboratory of Molecular Biology.Immunity and Inflammation, at Imperial College.Antimicrobial Defence Laboratory, at the Crick.Centre de Recherche, INSERM U932, Institut Curie.Cancer Inflammation and Immunity Group, at CRUK Manchester Institute, The University of Manchester.
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