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In-Depth Information
importance of proximity between these organelles has not been tested. It will be
interesting to address these questions in the future by expressing the AKAP450
domain that successfully disrupts Golgi-centrosome vicinity while leaving Golgi
organization and functionality intact (Hurtado et al.
2011
).
7.5 Functional Interactions Between the Golgi
and the Centrosome in Mitosis
At the onset of mitosis, the Golgi apparatus of mammalian cells undergoes
extensive reorganization. During this process, Golgi membranes lose their asso-
ciation with the centrosome, and are fragmented and dispersed throughout the
cytoplasm. This fragmentation process is initiated in G2 with the disconnection of
the non-compact zones of the Golgi ribbon and the generation of isolated, peri-
centrosomal mini-stacks (Colanzi et al.
2007
; Feinstein and Linstedt
2007
). This
step depends on the recruitment of the mitotic kinase Aurora A to the centrosome,
which, when blocked, prevents Golgi fragmentation and entry into mitosis (Persico
et al.
2010
). Next, in prophase, the isolated Golgi mini-stacks are converted into
tubular vesicular elements, called Golgi ''blobs''. This step is mediated by the
MAP kinase pathway components Raf1, MEK1, and Erk1c (Acharya et al.
1998
;
Colanzi et al.
2003b
; Shaul and Seger
2006
). Finally, Golgi ''blobs'' are broken
down into the so-called Golgi ''haze'' by a mechanism that involves the protein
kinases Plk1 and Cdc2 (Colanzi et al.
2003a
; Lowe et al.
1998
; Wei and Seemann
2009
; Sütterlin et al.
2001
). Upon completion of mitosis, Golgi fragments reas-
semble into the ribbon through the G- and C-stage steps that we have discussed
previously for experimentally induced Golgi fragmentation (Miller et al.
2009
).
During this entire multi-step Golgi disassembly process, Golgi membranes remain
separate and distinct from the ER (Jokitalo et al.
2001
; Pecot and Malhotra
2004
).
A number of studies support the existence of a functional link between the
Golgi and the centrosome during mitosis. For example, mitotic Golgi reorgani-
zation, during which the physical Golgi-centrosome connection is lost, was found
to be necessary for the regulation of cell cycle progression. When Golgi frag-
mentation was prevented by microinjection of GRASP65-related reagents, cells
arrested in G2 and did not enter mitosis (Sütterlin et al.
2002
). Preisinger and
colleagues obtained similar results when they overexpressed GRASP65 (Preisinger
et al.
2005
). The inhibitory effect of GRASP65 on mitotic entry was only seen with
wild-type GRASP65, and not with a non-phosphorylatable mutant, indicating that
excess GRASP65 may titrate out the activity of a kinase important for Golgi
fragmentation. Similarly, inhibiting the membrane fission protein CtBP3/BARS
prevented mitotic Golgi fragmentation and blocked cells from entering mitosis
(Hidalgo Carcedo et al.
2004
).
There are several possible explanations for the link between Golgi fragmentation
and mitotic entry. First, the conversion of the Golgi ribbon into smaller fragments
may facilitate the equal partitioning of this single-copy organelle into the two
