Biology Reference
In-Depth Information
required for centrosome separation (Glover et al.
1995
). The studies of Eg2 protein
function in Xenopus laevis cell-free extract have shown that Eg2 is associated
with centrosomes and involved in MTs' organization and spindle formation
(Roghi et al.
1998
). Very soon, it became clear that Eg2 was the homolog of D.
melanogaster Aurora-A kinase (Glover et al.
1995
; Giet et al.
1999a
,
b
). Since this
discovery the Aurora-A/Eg2 protein kinase was studied in parallel in Drosophila
and Xenopus embryo. Its activation was soon correlated with M-phase entry upon
Xenopus laevis oocyte entry into the meiotic maturation (Frank-Vaillant et al.
2000
). The primordial role of this kinase in oocyte maturation seems to be the
regulation of maternal mRNAs polyadenylation status (Mendez et al.
2000
;
Pascreau et al.
2005
). Aurora-A has been shown to regulate MT nucleation and
organization via phosphorylation of maskin/TACC (Pascreau et al.
2005
;
Kinoshita et al.
2005
) necessary for the MT-Associated (MAP) protein XMAP215
targeting to the centrosomes (Brittle and Ohkura
2005
). Aurora-A kinase was also
shown to phosphorylate kinesine Eg5 distributed along MTs (Giet et al.
1999a
).
Because Aurora-A has been recognized as an oncogene and a tumor suppressor,
depending on the cell type, the studies in Xenopus have an important impact on the
understanding of Aurora-A and centrosome functions in carcinogenesis.
20.5 Molecular Studies of Centrosome Duplication
in Xenopus laevis
Centrosome duplication has been extensively studied in Xenopus extract and
embryos allowing deciphering its regulation at the molecular level. The possible
disconnection between centrosome duplication and cell cycle progression was
observed using Xenopus embryos (stage blastula) treated with cycloheximide
(Gard et al.
1990
).
The second important breakthrough was the discovery of the control of cen-
trosome duplication by CDK/cyclin complexes, in particular, CDK2/cyclin E
(Lacey et al.
1999
) (Hinchcliffe et al.
1999
). It is, however, still unknown what
substrate(s) of CDK2/cyclin E is (are) necessary for this regulation. In Xenopus
egg extract, the duplication of centrosome was found to be sensitive to calcium
with a role of calmodulin and CaM kinase II in the initiation of duplication
(Matsumoto and Maller
2002
). As pointed out by the authors, these data provided a
link between cell cycle progression, calcium waves, and centrosome duplication.
Plk4, a divergent member of the Polo-like kinase family already mentioned
above, is another key molecule involved in centriole and centrosome duplication
(Bettencourt-Dias et al.
2005
; revieved by Sillibourne and Bornens
2010
). Little is
known how Plk4 control centriole duplication but the network of genes involved in
this process is steadily increasing. For instance, Hatch et al. (
2010
) have used
recently a ''kinase dead'' mutant of Plk4 expressed in the cell-free extract to screen
for Plk4 associated proteins. They identified seven proteins and among them
Cep152, the homolog of D. melanogaster Asterless (Asl gene product), already
