Annexins and Membrane Fusion - Fusion of Biological Membranes and Related Problems - page 98

occur (Drust and Creutz, 1988; Glenney, 1986). What is also clear is that
neither p11-binding nor complex formation are required for annexin II to
bind to endosomes, whereas both Ca 2+ and p11 are essential for targeting
of annexin II to the cytoskeleton (Jost et al., 1994). One possible model for
annexin II behaviour in this context is that following engagement of a
receptor by ligand, the rapid rise in cytosolic Ca 2+ drives annexin II to the
plasma membrane. At first, during the period of elevated Ca 2+ , the interac-
tion of annexin II with membranes conforms to the classical view of Ca 2+ -
dependent phospholipid-binding by annexins. However, in regions of
receptor internalization, annexin II would also form a stable association
with a protein or lipid component of newly formed endosomes. As this sec-
ondary interaction is Ca 2+ -independent annexin II would remain in the
endocytic compartment even after cytosolic Ca 2+ levels return to baseline.
There have also been reports of annexin II associated with p11 as a het-
erotetramer being involved in the fusion of endosomes (Harder and Gerke,
1993). It has also been suggested that annexin II bound to the endosome in
aCa 2+ -independent manner, in the absence of p11, could easily become
fusogenic by binding p11 following clathrin depolymerization and prior to
the formation of an early endosome.
Mayora et al. (1994) have shown that the combination of arachidonic
acid and purified annexin II can cause Ca 2+ -dependent fusion of endosomes
that have previously been washed with EDTA in a cell free system. At
micromolar concentrations of Ca 2+ , endosomes are still able to fuse with
each other. Fusion of endosomes was found to be inhibited half maximally
by the addition of an annexin II antibody. So there appear to be at least
two mechanisms by which endosomes fuse, one which is Ca 2+ -independent
and the other which is Ca 2+ -dependent, and may involve annexin II
(Mayorga et al., 1994). There may be an advantage to the cell in having these
different mechanisms, perhaps in determining the eventual destination of
the endocytic vesicle, as during phagocytosis it has been observed that
phagosomes can fuse directly with lysosomes in the presence of Ca 2+ (Jaconi
et al., 1990). This may also be important in regulating the different endo-
cytic routes taken by endosomes depending on which receptor has been
used for internalization (Joiner et al., 1989).
3.3. Annexin I
Like annexin II, annexin I has been found localized with early endo-
somes (Seemann et al., 1996) although in the latter case the association is
Ca 2+ -dependent. It is particularly interesting that during internalization of
activated EGF receptors, up to 38% of the total cellular annexin I (Pol et
al., 1997) becomes concentrated with the receptors in multivesicular bodies