Biology Reference
In-Depth Information
Table 7.2
Reported functional associations between the Golgi and the centrosome in mamma-
lian cells
Regulatory functions of
Golgi-centrosome
interactions
Dependent on
organelle
proximity?
References
Interphase: adjacent Golgi and centrosome
Cell polarization
Yes
Hurtado et al. (
2011
), Yadav et al. (
2009
)
Signaling Platforms
Not known
Doxsey et al. (2005), Wilson et al. (
2011
)
Centrosome organization
Not known
Kodani et al. (
2009
), Kodani and Sütterlin
(
2008
); Wilson et al. (
2011
)
Mitosis: separated Golgi and centrosome
Mitotic entry
Proximity has to be
disrupted
Hidalgo Carcedo et al. (
2004
), Preisinger
et al. (
2005
), Sütterlin et al. (
2002
)
Golgi ribbon formation
Not known
Wei and Seemann (
2009
)
Spindle formation
Not known
Chang et al. (
2005
), Liu et al. (
2008
),
Sütterlin et al. (
2005
), Zhang et al.
(
2011
)
cell polarization. Either the ribbon structure, or the position, or both, could be
contributing regulatory elements. To distinguish between these possibilities, one
would want to separate the two organelles without losing their structural and
functional integrity—i.e. to position an intact, interconnected Golgi ribbon away
from the centrosome. One can think of at least three different ways to achieve this
goal. First, a genetic screen could be performed, in which mutants that display a
physical separation of the Golgi and the centrosome are selected. However, Golgi-
centrosome proximity has predominantly been observed and studied in mamma-
lian cells, and such a genetic approach would therefore be highly complicated.
Second, small molecules could be screened for the specific phenotype of dis-
rupting Golgi-centrosome proximity. Natural compounds, such as Brefeldin A,
Norrisolide, and Ilimaquinone have been widely used to understand different
aspects of Golgi regulation (Guizzunti et al.
2006
; Lippincott-Schwartz et al.
1989
;
Takizawa et al.
1993
). However, to date, there is no compound that separates the
intact Golgi ribbon from the centrosome. We have recently identified a natural
compound with a completely novel Golgi disrupting activity (Schnermann et al.
2010
). This molecule, by the name of MacFarlandin E, converts the Golgi ribbon
into small fragments, but does not disperse them. The identification of a compound
with this remarkable and novel Golgi modifying activity gives hope that there may
be a compound that can specifically mislocalize the Golgi ribbon without altering
its overall organization and functionality. Third, interfering with Golgi-localized
proteins by RNAi-mediated depletion or by overexpression of dominant negative
forms could disrupt the Golgi-centrosome proximity. A recent study has suc-
cessfully used this approach. By overexpressing a fragment of the Golgi-associated
scaffolding protein AKAP450, Hurtado and colleagues managed to move the Golgi
ribbon away from the centrosome. Under these conditions, cell polarity and cell
migration was significantly reduced, demonstrating for the first time that the
pericentrosomal position of the Golgi ribbon is critical for the regulation of cell
