626
Biogenesis, Structure and Function of Lysosomes
5
Lysosomal Pathways of Proteolysis
There are several different pathways for
intracellular protein degradation. The ma-
jor pathway in the cytosol and nucleus is
the ubiquitin/proteasome system. Other
proteolytic systems in the cytosol include
calpains and caspases. Most cells also
exhibit a lysosomal component of proteoly-
sis, and six different pathways of lysosomal
proteolysis have been described in yeast
(Fig. 4) and mammalian cells (Fig. 5).
5.1
Endocytosis
Extracellular proteins such as hormones,
growth factors, and serum proteins can
be internalized by receptor-mediated en-
docytosis, absorptive endocytosis, or fluid-
phase endocytosis by both yeast (Fig. 4)
and mammalian cells (Fig. 5). Proteins
that are internalized by fluid-phase en-
docytosis do not interact with the plasma
membrane. Proteins that adsorb to plasma
membrane proteins or lipids or that bind to
plasma membrane receptors can be inter-
nalized at rates hundreds or thousands of
times more ef±ciently than by fluid-phase
endocytosis alone.
Endosomes
are
usually
coated
by
clathrin and AP-2 adaptor molecules. The
clathrin is uncoated by the constitutively
expressed
hsp70
(hsc70),
and
the
in-
ternalized material travels through early
endosomes, late
endosomes,
and
then
to the vacuole (Fig. 4) or to lysosomes
(Fig. 5) where they are degraded. In some
cells, the degradation begins in early or
late endosomes but is often completed
within lysosomes.
The endocytic pathway can also deliver
plasma membrane proteins to lysosomes
for degradation (Figs 4 and 5). For exam-
ple, the insulin receptor along with insulin
is degraded within lysosomes. Other recep-
tors may be spared lysosomal proteolysis
because they are recycled to the plasma
membrane. A growing number of plasma
membrane proteins in yeast and mam-
malian cells are delivered to lysosomes for
degradation only after a cytosolic domain
has been tagged by ubiquitin.
V
N
E
P
Vacuolar import and
degradation
Macroautophagy
APh
Microautophagy
Pexophagy
Endocytosis
Fig. 4
Vacuolar pathways of protein
degradation in yeast. N
=
nucleus;
V
=
vacuole; APh
=
autophagosome;
E
=
endosome; P
=
peroxisome. Four
different pathways for vacuolar
degradation of proteins, as listed in the
±gure and described in the text, have
been described in yeast. Pexophagy
refers to the microautophagic uptake of
peroxisomes by the yeast vacuole.
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