Biology Reference
In-Depth Information
Unlike others Apicomplexans, Theileria does not reside in a parasitophorous
vacuole. After it enters the host cell, it dissolves the membrane surrounding it and
sits naked in the cytoplasm surrounded just by a fuzzy layer of secreted material
(Shaw et al.
1991
; Jura et al.
1983
). It closely associates and interacts with host cell
microtubules (Shaw
2003
). The Theileria-associated host cell microtubules are
unusually stable as they are not affected by microtubule-disrupting agents that
cause microtubule disruption in uninfected cells (Shaw
2003
).
Within the host cell cytoplasm, the parasite undergoes serial asexual nuclear
multiplications and differentiates into a syncytium. The syncytium can divide and
redistribute itself into the two daughter lymphocytes. During lymphocyte cytoki-
nesis the parasite evolves to associate with the host mitotic spindle itself, thus
almost passively hitching a ride. Recently, von Schubert et al. (
2010
) described
how the parasite regulates host cell spindles to assure that each daughter cell
continues to be infected. This occurs by a direct regulation of host cell Polo-like
kinase (Plk) during parasite mitosis. Mitotic kinases are monitors of the cell cycle.
One of these key regulators is Cdk1. After inactivation of this kinase, Plk, which is
associated with kinetochores, dissociates from them and localizes to form the
central spindle. Regulatory proteins, such as Plk1, Aurora B, and some Rho
GTPases allow the central spindle to act as a platform that will form the plane of
cleavage during cytokinesis and initiate the process of cell division (Barr and
Gruneberg
2007
).
At the early mitotic phases, Theileria schizont binds to host cell spindle pole
microtubules. This allows the parasite to be directed to the equatorial region of the
dividing cell, the same region where host cell chromosomes are positioned. At this
stage, the parasite binds to astral as well as central microtubules by recruiting host
cell Plk, allowing parasite segregation during cytokinesis into the daughter cells.
Using inhibitors of the connection between the parasite and the spindle microtu-
bules, von Schubert et al. (
2010
) prevented parasite segregation, showing the
usurpation of the host cell mitotic machinery by Theileria to guarantee the con-
tinuity of itself in the daughter cells. During the abscission process, part of the
parasite is trapped as a slim tube. It remains to be determined whether parasite-
own structures provide its abscission or whether such signals are entirely derived
from the host cell. Once incorporated into the central spindle/midbody, the parasite
does not affect host cell central spindle function or abscission.
Eventually the Theileria syncytium undergoes a process called merogony,
where several parasites bud from this central mass; they are released afterwards,
infecting now erythrocytes (Shaw
2003
). This budding process as well as the
sequential nuclear division must be tightly regulated in order to form new mature,
infective parasites, containing all the organelles and with the correct nuclear
repertoire. In order to accomplish this, the organelles are tethered to the nuclear
membrane that is in turn connected to the parasite plasma membrane (Shaw and
Tilney
1992
). Thus, although little is known about the molecules involved, all
organelles are associated to each other, facilitating the distribution of the formed
daughter organelles into the budding parasites.
