Biology Reference
In-Depth Information
9.4.2 Centriole Disengagement
The final step in the centrosome cycle occurs in late mitosis when, at each spindle
pole, the centriole pair loses its tight orthogonal attachment. This process, origi-
nally called disorientation but now more commonly referred to as disengagement,
is a key licensing step for the next round of centriole duplication that will take
place in the subsequent cell cycle. While we know very little about the nature of
the ''glue'' that binds procentrioles to their parents, pathways that regulate dis-
engagement are beginning to emerge and, as for centriole duplication, there are
key roles for protein degradation.
Intriguingly, much of what has been learned about the regulation of disen-
gagement has come from the educated guess that the process of disengagement is
not dissimilar to that of sister chromatid segregation that also occurs in late
mitosis. The separation of sister chromatids results from the APC/C
Cdc20
-mediated
degradation of securin. This releases the cysteine protease, separase that in turn
cleaves the Scc1/kleisin subunit of cohesin. Having found that APC/C activity is
required for centriole disengagement in an in vitro disengagement assay estab-
lished in Xenopus egg extracts, Tsou and Stearns hypothesized that separase may
also play a key role in centriole disengagement (Tsou and Stearns
2006
).
Remarkably, they found that blocking separase activity in the egg extracts, either
with an excess of cyclin B that can bind and inhibit separase or non-degradable
securin, prevented centriole disengagement. A number of additional studies have
since provided persuasive evidence that release of active separase is what triggers
centriole disengagement in human cells (Thein et al.
2007
; Tsou et al.
2009
). Thus,
activation of the APC/C and destruction of securin at the metaphase-anaphase
transition provides an elegant mechanism of coupling the centrosome cycle with
the cell division cycle. Moreover, it ensures that the two centrioles within a single
spindle pole do not split apart until after the onset of chromosome segregation.
An obvious question is what separase cleaves to trigger centriole disengage-
ment. To separate sister chromatids, it cleaves the cohesin ring that encircles the
DNA sisters (Peters et al.
2008
; Nasmyth
2011
). It is not clear, though, how a ring
could hold centriole pairs together. Although one can conceive of concatenated
rings acting as a chain between the two centrioles, the most obvious solution, at
least at first, was that separase has a distinct target at the centrosome. However,
there is increasing evidence now for the existence of cohesin subunits at the
centrosome and Stemmann and colleagues have elegantly demonstrated that
ectopic cleavage of engineered cohesin rings can trigger centriole disengagement
(Schockel et al.
2011
). This highly provocative finding argues strongly that the
cohesin ring may indeed represent both the sister chromatid and centriole pair
''glue'' explaining why separase triggers both events simultaneously at the onset of
anaphase. However, the centrosomal protein, kendrin/pericentrin, has recently
been proposed as an alternative separase target whose cleavage promotes centriole
disengagement (Matsuo et al.
2012
).
