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

TRANSPORT INTO THE CELL FROM THE PLASMA MEMBRANE: ENDOCYTOSIS
739
unstimulated cell
insulin
receptor
EXTRACELLULAR
SPACE
CYTOSOL
glucose
glucose
transporter
insulin-stimulated cell
insulin
intracellular
signal
glucose
Figure 13–59 Storage of plasma
membrane proteins in recycling
endosomes. Recycling endosomes can
serve as an intracellular storage site for
specialized plasma membrane proteins
that can be mobilized when needed. In
the example shown, insulin binding to the
insulin receptor triggers an intracellular
signaling pathway that causes the rapid
insertion of glucose transporters into the
plasma membrane of a fat or muscle cell,
greatly increasing its glucose intake.
intracellular pool of glucose
transporters in specialized
recycling endosomes
signal causes relocalization
of glucose receptors to
plasma membrane to boost
glucose uptake into the cell
Phagocytosis is important in most animals for purposes other than nutrition,
and it is carried out mainly by specialized cells—so-called professional phagocytes.
In mammals, two important classes of white blood cells that act as professional
phagocytes are macrophages and neutrophils (Movie 13.5). These cells develop
from hemopoietic stem cells (discussed MBoC6 m13.61/13.60 in Chapter 22), and they ingest invading
microorganisms to defend us against infection. Macrophages also have an
important role in scavenging senescent cells and cells that have died by apoptosis
(discussed in Chapter 18). In quantitative terms, the clearance of senescent and
dead cells is by far the most important: our macrophages, for example, phagocytose
more than 10 11 senescent red blood cells in each of us every day.
The diameter of a phagosome is determined by the size of its ingested particles,
and those particles can be almost as large as the phagocytic cell itself (Figure
13–60). Phagosomes fuse with lysosomes, and the ingested material is then
degraded. Indigestible substances remain in the lysosomes, forming residual bodies
that can be excreted from cells by exocytosis, as mentioned earlier. Some of the
internalized plasma membrane components never reach the lysosome, because
they are retrieved from the phagosome in transport vesicles and returned to the
plasma membrane.
Some pathogenic bacteria have evolved elaborate mechanisms to prevent
phagosome–lysosome fusion. The bacterium Legionella pneumophila, for example,
which causes Legionnaires’ disease (discussed in Chapter 23), injects into
its unfortunate host a Rab-modifying enzyme that causes certain Rab proteins
to misdirect membrane traffic, thereby preventing phagosome–lysosome fusion.
The bacterium, thus spared from lysosomal degradation, remains in the modified
phagosome, growing and dividing as an intracellular pathogen, protected from
the host’s adaptive immune system.
Phagocytosis is a cargo-triggered process. That is, it requires the activation of
cell-surface receptors that transmit signals to the cell interior. Thus, to be phagocytosed,
particles must first bind to the surface of the phagocyte (although not
all particles that bind are ingested). Phagocytes have a variety of cell surface
receptors that are functionally linked to the phagocytic machinery of the cell.
The best-characterized triggers of phagocytosis are antibodies, which protect us
by binding to the surface of infectious microorganisms (pathogens) and initiating
a series of events that culminate in the invader being phagocytosed. When
antibodies initially attack a pathogen, they coat it with antibody molecules that
bind to Fc receptors on the surface of macrophages and neutrophils, activating
the receptors to induce the phagocytic cell to extend pseudopods, which engulf
the particle and fuse at their tips to form a phagosome (Figure 13–61A). Localized
actin polymerization, initiated by Rho family GTPases and their activating Rho-
GEFs (discussed in Chapters 15 and 16), shapes the pseudopods. The activated
Rho GTPases switch on the kinase activity of local PI kinases to produce PI(4,5)P 2
in the membrane (see Figure 13–11), which stimulates actin polymerization. To
seal off the phagosome and complete the engulfment, actin is depolymerized by a
PI 3-kinase that converts the PI(4,5)P 2 to PI(3,4,5)P 3 , which is required for closure
5 µm
Figure 13–60 Phagocytosis by a
macrophage. A scanning electron
micrograph of a mouse macrophage
phagocytosing two chemically altered red
blood MBoC6 cells. The m13.46/13.61
red arrows point to edges
of thin processes (pseudopods) of the
macrophage that are extending as collars
to engulf the red cells. (Courtesy of Jean
Paul Revel.)