W
e have used in vivo and in vitro strategies to study
the mechanisms of
multivesicular en
dosomes
biogenesis
.
We f
ou
nd
that, while
annexinA2
and
Arp2/3
mediate
F
-
actin
nucleation and
branching,
respectively
,
the ERM protein
moesin
support
s
the
formation of F
-
actin
networks
on early endosom
es
.
We also
f
ound
that
moesin
plays no role during endoc
ytosis and recycling to the plasma
membrane
,
but
is
absolutely
required, much like actin,
for early
-
to
-
late endosome
transport and multivesicular endosome
formation
.
Both a
ctin network formation in
vitro and early
-
to
-
late endosome transport in vivo also de
pend on the F
-
actin
binding protein cortactin.
O
ur data
thus
show
that
moesin and cortactin are
necessary for
the
formation of F
-
actin
networks
that mediate endosome
biogenesis
—
or
maturation
—
and
transport
through the degradative pathway
.
We
propose
tha
t
the
primary function of
endosomal
F
-
actin
is to
control
the
membrane remodeling process that accompanies endosome biogenesis
.
We
also
speculate that this
mechanism
helps
segregate tubular and multivesicular
membranes along the recycling and degradation p
athways, respectively.