Parasitophorous vacuoles (PV) that harbour Leishmania
parasites acquire some characteristics from
fusion with host cell vesicles. Recent studies have
shown that PVs acquire and display resident endoplasmic
reticulum (ER) molecules. We investigated
the importance of ER molecules to PV biology by
assessing the consequence of blocking the fusion
of PVs with vesicles that originate from the early
secretory pathway. This was achieved by targeting
the N-ethylmaleimide-sensitive factor attachment
protein receptors (SNAREs) that mediate the
fusion of early secretory vesicles. In the presence
of dominant negative variants of sec22b or some of
its known cognate partners, D12 and syntaxin 18,
PVs failed to distend and harboured fewer parasites.
These observations were confirmed in
studies in which each of the SNAREs listed above
including the intermediate compartment ER/Golgi
SNARE, syntaxin 5, was knocked down. The
knock-down of these SNARES had little or no measurable
effect on the morphology of the ER or on
activated secretion even though they resulted in a
more significant reduction of PV size. Moreover,
the knock-down of the ER/Golgi SNAREs resulted
in significant reduction in parasite replication.
Taken together, these studies provide further evidence
that PVs acquire ER components by fusing
with vesicles derived from the early secretory pathway; disruption of this interaction results in
inhibition of the development of PVs as well as the
limitation of parasite replication within infected
cells
