Essential Cell Biology 5th edition

Endocytic Pathways
525
shed their coat and fuse with an endosome. Extracellular fluid is trapped
in the coated pit as it invaginates to form a coated vesicle, and so substances
dissolved in the extracellular fluid are internalized and delivered
to endosomes. This fluid intake by clathrin-coated and other types of
pinocytic vesicles is generally balanced by fluid loss during exocytosis.
Receptor-mediated Endocytosis Provides a Specific
Route into Animal Cells
Pinocytosis, as just described, is indiscriminate. The endocytic vesicles
simply trap any molecules that happen to be present in the extracellular
fluid and carry them into the cell. However, pinocytosis can sometimes
be more selective. In most animal cells, specific macromolecules can
be taken up from the extracellular fluid via clathrin-coated vesicles. The
macromolecules bind to complementary receptors on the cell surface and
enter the cell as receptor–macromolecule complexes in clathrin-coated
vesicles (see Figure 15–21). This process, called receptor-mediated
endocytosis, provides a selective concentrating mechanism that
increases the efficiency of internalization of particular macromolecules
more than 1000-fold compared with ordinary pinocytosis, so that even
minor components of the extracellular fluid can be taken up in large
amounts without taking in a correspondingly large volume of extracellular
fluid. Such is the case when animal cells import the cholesterol they
need to make new membrane.
Cholesterol is a lipid that is extremely insoluble in water (see Figure 11−7).
It is transported in the bloodstream bound to proteins in the form of particles
called low-density lipoproteins, or LDL. Cholesterol-containing LDLs,
which are secreted by the liver, bind to receptors located on the surface
of cells. The resulting receptor–LDL complexes can then be ingested by
receptor-mediated endocytosis and delivered to endosomes. The interior
of endosomes is more acidic than the surrounding cytosol or the extracellular
fluid, and in this acidic environment the LDL dissociates from its
receptor: the empty receptors are returned, via transport vesicles, to the
plasma membrane for reuse, while the LDL is delivered to lysosomes.
In the lysosomes, the LDL is broken down by hydrolytic enzymes. Freed
from the bulky LDLs, cholesterol escapes into the cytosol, where it can be
used to synthesize new membrane (Figure 15−33).
LDL
clathrincoated
vesicle
LDL receptors
ENDOCYTOSIS
UNCOATING
FUSION WITH
ENDOSOME
hydrolytic
enzymes
plasma
membrane
EXTRACELLULAR SPACE
endosome
lysosome
CYTOSOL
DELIVERY OF LDL
TO LYSOSOME
BUDDING OFF
OF TRANSPORT VESICLES
free
cholesterol
RETURN OF LDL
RECEPTORS TO
PLASMA
MEMBRANE
Figure 15−33 LDL enters cells via
receptor-mediated endocytosis. LDL
binds to LDL receptors on the cell surface
and is internalized in clathrin-coated
vesicles. The vesicles lose their coat and
then fuse with endosomes. In the acidic
environment of the endosome, LDL
dissociates from its receptors. The LDL ends
up in lysosomes, where it is degraded to
release free cholesterol (red dots), while the
LDL receptors are returned to the plasma
membrane via transport vesicles to be used
again (Movie 15.12). For simplicity, only
one LDL receptor is shown entering the cell
and returning to the plasma membrane.
Whether it is occupied or not, an LDL
receptor typically makes one round trip
into the cell and back every 10 minutes,
making a total of several hundred trips
over its 20-hour life-span.