Molecular Biology of the Cell by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morgan, Martin Raff, Keith Roberts, Peter Walter by by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morg

740 Chapter 13: Intracellular Membrane Traffic
bacterium
pseudopod
plasma
membrane
(B)
bacterium
actin
PI(4,5)P 2
PI(3,4,5)P 3
PI 3-kinase
Figure 13–61 A neutrophil reshaping
its plasma membrane during
phagocytosis. (A) An electron micrograph
of a neutrophil phagocytosing a
bacterium, which is in the process of
dividing. (B) Pseudopod extension and
phagosome formation are driven by actin
polymerization and reorganization, which
respond to the accumulation of specific
phosphoinositides in the membrane
of the forming phagosome: PI(4,5)P 2
stimulates actin polymerization, which
promotes pseudopod formation, and then
PI(3,4,5)P 3 depolymerizes actin filaments
at the base. (A, courtesy of Dorothy F.
Bainton, Phagocytic Mechanisms in Health
and Disease. New York: Intercontinental
Medical Book Corporation, 1971.)
phagocytic
white blood cell
(A)
1 µm
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
MBoC6
that inhibit
m13.47/13.62
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.
Summary
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