Biology Reference
In-Depth Information
single copy of the duplicated genome and one centrosome into each of two daughter
cells. Like the genome the single centrosome must be duplicated, and to ensure
formation of a bipolar mitotic spindle must not be duplicated again until the fol-
lowing cell cycle. Just as regulated proteolysis prevents the re-initiation of DNA
replication, failing to properly destroy critical centrosome regulators leads to the
production of excess centrosomes. Many aspects of centrosome duplication and
function are controlled by protein degradation, and multiple protein degradation
pathways are found at centrosomes, and in some cases the relevant destruction event
occurs explicitly at centrosomes. Here, we discuss the various degradation
machineries found at centrosomes, and the many ways in which centrosome biology
is controlled by protein degradation.
8.2 The Centrosome
The centrosome is best known as a microtubule organizing center (MTOC).
Centrosomes consist of a pair of centrioles, which are cylinders composed of
nine radially symmetric triplet microtubules [reviewed in (Adams and Kilmartin
2000
; Tsou and Stearns
2006
)]. The central centriole pair is surrounded by a
pericentriolar matrix (PCM) that is responsible for microtubule nucleation. As
MTOCs, centrosomes function as spindle poles during mitosis, and in order to
ensure faithful chromosome segregation centrosome number must be strictly
controlled to ensure the assembly of a bipolar mitotic spindle (Fisk et al.
2002
).
Centrosome number is controlled through the tightly regulated process of cen-
trosome duplication wherein a single new centriole is assembled at a site
adjacent to each existing centriole [reviewed in (Azimzadeh and Marshall
2010
;
Pike and Fisk
2011
)]. Centrosome duplication has many analogies with DNA
replication, both of which are semi-conservative processes initiated by Cdk2. A
vast amount of work in the past handful of years has identified a large number
of centriolar and centrosomal proteins whose activities are coordinated to ensure
that only two new centrioles are assembled in any given cell cycle [reviewed in
(Pike and Fisk
2011
)]. A proteomic analysis of the human centrosome identified
hundreds of proteins (Andersen et al.
2003
), while comparative genomics
identified a set of genes likely to encode proteins that specifically function at
basal bodies, cilia, and flagella (Li et al.
2004
), and a combination of the two
approaches using green algae identified a core set of centriolar proteins (Keller
et al.
2005
). Genome wide RNAi studies in C. elegans identified a core set of
genes required for the assembly of new centrioles (Delattre et al.
2006
; Pelletier
et al.
2006
), and live cell imaging in embryos led to the assignment of these
proteins into an ordered centriole assembly pathway that is conserved in
organisms as distinct as ciliated protazoa and humans (Delattre et al.
2006
;
Pelletier et al.
2006
; Dammermann et al.
2004
; Leidel and Gonczy
2005
;
O'Connell
2002
; Kemp et al.
2004
): Cdk2 regulates the targeting of Spd-2, the
first protein known to arrive at the site of centriole assembly. The Zyg1 protein
