PI(4,5)P2 PI(3,4,5)P3 of the phagosome and may also contribute to reshaping the actin network to help drive the invagination of the forming phagosome (Figure 13–61B). In this way, the ordered generation and consumption of specific phosphoinositides guides sequential steps in phagosome formation.
Several other classes of receptors that promote phagocytosis have been characterized. Some recognize complement components, which collaborate with antibodies in targeting microbes for destruction (discussed in Chapter 24). Others directly recognize oligosaccharides on the surface of certain pathogens. Still others recognize cells that have died by apoptosis. Apoptotic cells lose the asymmetric distribution of phospholipids in their plasma membrane. As a consequence, negatively charged phosphatidylserine, which is normally confined to the cytosolic leaflet of the lipid bilayer, is now exposed on the outside of the cell, where it helps to trigger the phagocytosis of the dead cell.
Remarkably, macrophages will also phagocytose a variety of inanimate particles—such as glass or latex beads and asbestos fibers—yet they do not phagocytose live cells in their own body. The living cells display “don’t-eat-me” signals in the form of cell-surface proteins that bind to inhibiting receptors on the surface of macrophages. The inhibitory receptors recruit tyrosine phosphatases that antagonize the intracellular signaling events required to initiate phagocytosis, thereby locally inhibiting the phagocytic process. Thus phagocytosis, like many other cell processes, depends on a balance between positive signals that activate the process and negative signals that inhibit it. Apoptotic cells are thought both to gain “eat-me” signals (such as extracellularly exposed phosphatidylserine) and to lose their “don’t-eat-me” signals, causing them to be very rapidly phagocytosed by macrophages.
Cells ingest fluid, molecules, and particles by endocytosis, in which localized regions of the plasma membrane invaginate and pinch off to form endocytic vesicles. In most cells, endocytosis internalizes a large fraction of the plasma membrane every hour. The cells remain the same size because most of the plasma membrane components (proteins and lipids) that are endocytosed are continually returned to the cell surface by exocytosis. This large-scale endocytic–exocytic cycle is mediated largely by clathrin-coated pits and vesicles but clathrin-independent endocytic pathways also contribute.
While many of the endocytosed molecules are quickly recycled to the plasma membrane, others eventually end up in lysosomes, where they are degraded. Most of the ligands that are endocytosed with their receptors dissociate from their receptors