Biogenesis, Structure and Function of Lysosomes
625
Endocytosis
Cytoplasm-
to-vacuole
targeting
Vacuolar
inheritance
Macroautophagy
G
N
V
N
ALP
APh
CPY
PM
MVB
E
Fig. 3
Pathways for assembly of the vacuole in yeast. G
=
Golgi;
APh
=
autophagosome; ALP
=
alkaline phosphatase;
CPY
=
carboxypeptidase Y; E
=
endosome; MVB
=
multivesicular
body; V
=
vacuole; PM
=
plasma membrane; N
=
nucleus. Pathways
of vacuolar assembly and vacuolar inheritance are described in the text.
3.3
Vacuolar Inheritance
Vacuolar inheritance by daughter cells is
initiated by a protrusion of the vacuole
into
the
bud
region.
This
protrusion
vesiculates, and the vesicles move into
the bud (Fig. 3). The vesicles eventually
fuse to form the vacuole for the daughter
cell.
4
The Importance of Phosphoinositides in
Lysosomal Biogenesis
The
lysosomal
biogenesis
pathways
in
mammalian cells and the vacuolar bio-
genesis pathways in yeast require phos-
photidylinositol
(PI)
lipids.
Phosphory-
lation
of
PI
to
phosphotidylinositol-3-
phosphate
(PI3P)
can
be
inhibited
by
compounds
such
as
wortmannin
and
3-methyladenine. These inhibitors block
lysosomal biogenesis and disrupt several
different membrane traf±cking processes.
For example, both macroautophagy and
endocytosis are inhibited by these com-
pounds. PI3P acts at least in part by
binding
to
proteins
that
are
required
for vesicular traf±c. Some of these pro-
teins contain Fab1, YGLO23, Vps27, EEA1
(FYVE) domains that bind PI3P. Different
FYVE proteins are involved in different
steps of vesicular traf±c, docking, and fu-
sion both in mammalian and in yeast cells.
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