Movement of Molecules Across Cell Membranes
113
a conformational change when it binds a ligand. Through a
series of steps, a cytosolic protein called
clathrin
is recruited
to the plasma membrane. Clathrin forms a cage-like struc-
ture that leads to the aggregation of ligand-bound receptors
into a localized region of membrane, forming a depression, or
clathrin-coated pit,
which then invaginates and pinches off
to form a clathrin-coated vesicle. By localizing ligand-recep-
tor complexes to discrete patches of plasma membrane prior to
endocytosis, cells may obtain concentrated amounts of ligands
without having to engulf large amounts of extracellular fl
uid
from many different sites along the membrane. Receptor-
mediated endocytosis, therefore, leads to a selective concen-
tration in the endocytotic vesicle of a specifi c ligand bound to
one type of receptor.
Cholesterol is one example of a ligand that enters cells via
clathrin-dependent, receptor-mediated endocytosis. Cholesterol
is an important building block for plasma- and intracellular
membranes, and most cells require a steady supply of this mol-
ecule. Cholesterol circulates in the blood, bound with pro-
Vesicle
Solutes
Extracellular fluid
Extracellular fluid
Phagosome
Lysosome
Nucleus
Nucleus
Vesicle
formation
Pseudopodia
Bacterium
Plasma
membrane
Nonspecific
uptake of
solutes
and H
2
O
(a)
Fluid endocytosis
(b)
Phagocytosis
Lysosome
Cytosol
Golgi
apparatus
Ligand
Receptor
Receptors recycled
to membrane
Endosome
Receptors
Unbound
ligands
Clathrin proteins
forming a
clathrin-
coated pit
Clathrin proteins
being released
from vesicle
Vesicle
Nucleus
(c)
Receptor-mediated endocytosis
Figure 4–21
Types of endocytosis. (a) In fl uid endocytosis, solutes and water are nonspecifi cally brought into the cell from the extracellular fl
uid via
endocytotic vesicles. (b) In phagocytosis, specialized cells form extensions of the plasma membrane called pseudopodia, which engulf bacteria
or other large objects such as cell debris. The vesicles that form fuse with lysosomes, which contain enzymes and other molecules that destroy
the vesicle contents. (c) In receptor-mediated endocytosis, a cell recognizes a specifi c extracellular ligand that binds to a plasma membrane
receptor. The binding triggers endocytosis. In the example shown here, the ligand-receptor complexes are internalized via clathrin-coated
vesicles, which merge with endosomes. Ligands may be routed to the Golgi apparatus for further processing, or to lysosomes. The receptors are
typically recycled to the plasma membrane.
teins in particles called lipoproteins. The protein components
of lipoproteins are recognized by plasma membrane receptors.
When the receptors bind the lipoproteins, endocytosis ensues
and the cholesterol is delivered to the intracellular fl
uid. The
rate at which this occurs can be regulated. For example, if a
cell has suffi cient supplies of cholesterol, the rate at which it
replenishes its supply of lipoprotein receptors may decrease.
Conversely, receptor production increases when cholesterol
supplies are low. This is a type of negative feedback that acts to
maintain the cholesterol content of the cell within a homeo-
static range.
Once an endocytotic vesicle pinches off from the plasma
membrane in receptor-mediated endocytosis, the clathrin coat
is removed and clathrin proteins are recycled back to the mem-
brane. The vesicles then have several possible fates, depending
upon the cell type and the ligand that was engulfed. Some
vesicles fuse with the membrane of an intracellular organelle,
adding the contents of the vesicle to the lumen of that organ-
elle. Other endocytotic vesicles pass through the cytoplasm
and fuse with the plasma membrane on the opposite side of
the cell, releasing their contents to the extracellular space. This
provides a pathway for the transfer of large molecules, such as
proteins, across the layers of cells that separate two fl
uid com-
partments in the body (for example, the blood and interstitial
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