Biology Reference
In-Depth Information
Plasmodium thus has different stages that undergo intense cell division, indi-
cating that an effective cell cycle control process is present. This intense repli-
cation within a brief period of time is critical for the survival and further
transmission of malaria parasites. Interestingly, the parasite multiplication in the
erythrocytes generates variable numbers of daughter cells (between 18-24),
probably because the different copies of the nucleus divide at different moments
during schizogony (Read et al.
1993
). This gives the impression that the cell cycle
control works differently than the ones characterized in higher eukaryotes, which
is controlled and synchronized by cyclin and cyclin-dependent kinases (CDKs)
that are differently expressed throughout the division process. In Plasmodium, the
regulatory mechanisms of the CDKs in the cell cycle are still largely not under-
stood (Doering et al. 2008). Inhibitors of higher eukaryotic CDKs can interfere
with Plasmodium (PfCDK), indicating that structural features required for inhi-
bition are conserved in these kinases (Graeser et al.
1996
; Li et al.
2001
; Holton
et al.
2003
).
Due to their roundish shape and apparent lack of polarity, the intracellular
stages of Plasmodium are not infective during schizogony. This is in contrast to the
related parasite Toxoplasma that maintains some of its infectiveness during the
division process (discussed below). Also different from Toxoplasma, Plasmodium
does not present clear centrioles but has spindle pole plaques for chromosomal
division (Morrissette and Sibley
2002a
; Gerald et al.
2011
).
Within a liver cell the parasite undergoes sequential nuclear divisions to form a
multinuclear syncytium containing thousands of nuclei. After 2-3 days, the nuclei
move to the periphery of the schizont and associate with the newly assembled
inner membrane complex, the subpellicular microtubules, and other apical orga-
nelles (Striepen et al.
2007
). The next generation of parasites starts to be formed
with a sequential invagination process of the mother-parasite membrane (Sturm
et al.
2009
) and is concluded when these new parasites begin to bud into the PV
matrix. The parasites ultimately destroy the PV membrane and are released into
the host cell cytoplasm from where they bleb off in carriers into the blood stream
(Sturm et al.
2006
). There are no experimental data available as to the molecular
components or mechanisms governing these interesting steps of the Plasmodium
life cycle despite the recognized medical importance of the liver stage for disease
prevention (Borrmann and Matuschewski
2011
).
During the early erythrocytic part of the cycle, unpolymerized tubulin is dis-
tributed diffusely within the parasite cytoplasm. Later a centrocone (alternatively
named centriolar plaque or spindle pole body or spindle pole plaque) is formed at
the nuclear membrane. This structure then divides into two identical parts that
migrate in opposite directions and form the spindle. Long and short intranuclear
microtubules connect the two halves within the nucleus; at the cytoplasmic side an
electron-dense material accumulates. In later stages of schizogony, cytoplasmic
microtubules associate with each nucleus forming a radial arrangement and
extending to the central zone of the parasite. The nuclei divide at different
moments during schizogony, which allows the observation of mitotic spindles at
distinct
developmental
stages
within
a
single
schizont
(Read
et
al.
1993
).
