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

732 Chapter 13: Intracellular Membrane Traffic
(A)
Figure 13–49 Caveolae in the plasma
membrane of a fibroblast. (A) This
electron micrograph shows a plasma
membrane with a very high density of
caveolae. (B) This rapid-freeze deep-etch
image demonstrates the characteristic
“cauliflower” texture of the cytosolic face of
the caveolae membrane. The characteristic
texture is thought to result from aggregates
of caveolins and cavins. A clathrin-coated
pit is also seen at the upper right. (Courtesy
of R.G.W. Anderson, from K.G. Rothberg
et al., Cell 68:673–682, 1992. With
permission from Elsevier.)
(B)
0.2 µm
in cholesterol, glycosphingolipids, and glycosylphosphatidylinositol (GPI)-anchored
membrane proteins (see Figure 10–13). The major structural proteins in
caveolae are caveolins, a family of unusual integral membrane proteins that each
insert a hydrophobic loop into the membrane from the cytosolic side but do not
extend across the membrane. On their cytosolic side, caveolins are bound to large
protein complexes of caving proteins, which are thought to stabilize the membrane
curvature. MBoC6 m13.49/13.49
In contrast to clathrin-coated and COPI- or COPII-coated vesicles, caveolae
are usually static structures. Nonetheless, they can be induced to pinch off and
serve as endocytic vesicles to transport cargo to early endosomes or to the plasma
membrane on the opposite side of a polarized cell (in a process called transcytosis,
which we discuss later). Some animal viruses such as SV40 and papillomavirus
(which causes warts) enter cells in vesicles derived from caveolae. The viruses are
first delivered to early endosomes and move from there in transport vesicles to the
lumen of the ER. The viral genome exits across the ER membrane into the cytosol,
from where it is imported into the nucleus to start the infection cycle. Cholera
toxin (discussed in Chapters 15 and 19) also enters the cell through caveolae and
is transported to the ER before entering the cytosol.
Macropinocytosis is another clathrin-independent endocytic mechanism
that can be activated in practically all animal cells. In most cell types, it does
not operate continually but rather is induced for a limited time in response to
cell-surface receptor activation by specific cargoes, including growth factors, integrin
ligands, apoptotic cell remnants, and some viruses. These ligands activate a
complex signaling pathway, resulting in a change in actin dynamics and the formation
of cell-surface protrusions, called ruffles (discussed in Chapter 16). When
ruffles collapse back onto the cell, large fluid-filled endocytic vesicles form, called
macropinosomes (Figure 13–50), which transiently increase the bulk fluid uptake
of a cell by up to tenfold. Macropinocytosis is a dedicated degradative pathway:
macropinosomes acidify and then fuse with late endosomes or endolysosomes,
without recycling their cargo back to the plasma membrane.
Cells Use Receptor-Mediated Endocytosis to Import Selected
Extracellular Macromolecules
In most animal cells, clathrin-coated pits and vesicles provide an efficient pathway
for taking up specific macromolecules from the extracellular fluid. In this
process, called receptor-mediated endocytosis, the macromolecules bind to