Endocytosis

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Lecture 36 Endocytosis pages 746 - 756
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Endocytosis is a process by which cells take up
substances by invaginating the plasma membrane.
This process can capture both membrane bound and
soluble components.

• Three types of endocytosis
• Phagocytosis takes up large particles and cells.
• Pinocytosis continuously takes up small amounts
  of fluid.
• Receptor-mediated endocytosis selectively takes
  up membrane receptors and associated ligands.

Endocytosis takes up large amounts of the plasma
membrane and is balanced by the return of
membrane components to the plasma membrane by
exocytosis.
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Phagocytosis is performed primarily by white
blood cells called Macrophages, Neutrophils, and
Dendritic cells. These cells have receptors in
the plasma membrane to recognize their targets.
For example, macrophages have receptors that
recognizes phosphatidylserine which becomes
exposed on the surface of dead cells.
This image is by a scanning electron microscope.
The technique is used to give information about
the surface of a sample because it monitors
electrons that reflect off of the surface.
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TEM image of a neutrophil phagocytosing a
bacteria.
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Pinocytosis allows the cell to take up small
portions of extracellular fluid. It occurs
continuously resulting in the cell ingesting 25
its total volume of fluid and 2X the surface of
the PM per hour. An equal rate of exocytosis
occurs so the cell size remains constant.
Clathrin-mediated pinocytosis occurs a structures
in the membrane called clathrin-coated pits.
Caveolin is a transmembrane protein that mediates
pinocytosis at structures called caveolae. The
caveolae are formed from lipid rafts.
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Receptor mediated endocytosis involves
transmembrane receptors that bind specific
ligands. The ligand-specificity of receptors
allows the cell to control the uptake of
particular ligands, and the distribution of these
ligands in the cell. Transport vesicles fuse
with the early endosome where the ligands and
receptors are sorted and then transported to
other destinations.
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Receptor mediated endocytosis is initiated at
clathrin-coated pits. Transmembrane receptors
bind ligands on the outside surface of the cell
and collect in coated pits via interactions with
adaptins and clathrin inside the cell. A single
coated pit can accumulate many different types of
receptors. The receptor-ligand complexes gather
in a small area so become highly concentrated in
transport vesicles.
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Uptake of low-density lipoproteins (LDL) is one
of the best understood examples of
receptor-mediated endocytosis. LDL is a
protein-lipid complex that transports
cholesterol-fatty acid esters in the blood
stream. LDL normally supplies cholesterol to
cells. Defects in the endocytic process result
in high blood levels of LDL. High LDL
predisposes individuals for atherosclerosis.
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Normally, LDL binds the receptor and the
receptors collect in coated pits through
association with adaptins and clathrin.
Some individuals have defects in the cytoplasmic
domain recognized by adaptin so the receptors
never collect in the coated pits.

• Other genetic defects that result in elevated
  blood levels of LDL
• absence of LDL receptor.
• defective LDL-binding site in the LDL receptor.

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In the case of LDL, LDL ultimately goes to the
lysosome and the LDL receptor is recycled back to
the PM.
pH 6 induces dissociation
Multivesicular body
Late endosome
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Endocytosed molecules that are destined for the
lysosome, such as LDL, go from the early
endosome to the multivesicular body to the late
endosome. Transport vesicles carrying acid
hydrolases from the Golgi fuse with the late
endosome causing the late endosome to mature into
a lysosome.
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In some cases, both the receptor and the ligand
are transported to the lysosome. This is the
case for EGF and its receptor. EGF (epidermal
growth factor) triggers a cell to proliferate but
the signal is only required for a short time.
Hence, both the ligand and the receptor are
destroyed.
Late endosome
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Why do cells use a multivesicular body rather
than using vesicular transport? It provides a
mechanism for exposing the cytoplasmic domain of
a receptor to the inside of the lysosome.
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Transcytosis combines endocytosis and exocytosis
to deliver some molecules across an epithelium.
Transport of antibodies in milk across the gut
epithelium of baby rats.
Acidic pH of the gut favor association of
antibody with Fc receptor whereas the neutral pH
of the extracellular fluid favors dissociation.