![]() One intracellular membrane transportation pathway known to translocate endosomes from the cell centre to the periphery is the Protrudin pathway. Despite substantial knowledge about the internal membrane sources in phagocytosis, the mechanism behind the translocation of vesicles to forming phagosomes is not known. During phagocytosis, VAMP7-mediated fusion of endosomes with the PM is dependent on Ca 2+ release from lysosomes and regulated by the Ca 2+ sensor Synaptotagmin VII (SYT7), which is enriched on lysosomes. Recycling endosomes containing the SNARE protein VAMP3 and late endosomes and lysosomes (LELys) positive for TI-VAMP/VAMP7 (VAMP7) are known membrane sources for phagocytic cup formation. To cope with engulfment of relatively large particles such as apoptotic bodies, the cell can instruct intracellular membranes to fuse with the PM to increase the surface area by focal exocytosis. Some organs rely on efferocytosis for proper function, like the eye’s retina, where retinal pigment epithelial (RPE) cells daily engulf photoreceptor outer segments to avoid blindness. Defects in the efferocytosis machinery can lead to autoimmune diseases, cancer, and neurodegenerative diseases. In this manner, phagocytes can discriminate between living and dead cells. Dying or dead cells expose various forms of the lipid phosphatidylserine (PS), which is recognised by receptors on the phagocyte. Non-professional phagocytes such as epithelial cells, endothelial cells and fibroblasts can remove dead cells, in a process termed efferocytosis. Upon binding to a particle, the plasma membrane (PM) will form pseudopods, also called a phagocytic cup, to surround and engulf the object. Phagocytosis is defined as a receptor-mediated engulfment of large particles (≥ 0.5 µm) such as pathogens and dead cells. Thus, the Protrudin pathway delivers endosomes to facilitate formation of the phagocytic cup important for PS-dependent phagocytosis. ![]() Conversely, Protrudin depletion or abrogation of ER-endosome contact sites inhibited phagocytic cup formation resulting in reduced uptake of PS-coated beads. Overexpression of Protrudin also led to elevated uptake of silica beads coated with PS. Exogenous addition of apoptotic bodies increased the formation of phagocytic cups, which further increased when Protrudin was overexpressed. RPE1 cells perform phagocytosis of dead cells (efferocytosis) that expose phosphatidylserine (PS) on their surface. Protrudin-dependent phagocytic cup formation required SYT7, which promotes fusion of LELys with the plasma membrane. Here, we show that Protrudin-mediated endoplasmic reticulum (ER)-endosome contact sites facilitate anterograde translocation of FYCO1 and VAMP7-positive late endosomes and lysosomes (LELys) to forming phagocytic cups in a retinal pigment epithelial-derived cell line (RPE1). ![]() However, how these vesicles are delivered to the phagocytic cup and the phagosome has been unknown. During phagocytosis, endosomes both contribute with membrane to forming phagosomes and promote phagosome maturation.
0 Comments
Leave a Reply. |
Details
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |