Biology Reference
In-Depth Information
by the Golgi and the centrosome. The most prominent example is the nucleation of
microtubules that we discussed previously. Interestingly, microtubule nucleation at
the Golgi and the centrosome depends on the same protein, the large scaffolding
protein AKAP450, which associates with both organelles and recruits c-tubulin as
the microtubule nucleation factor (Rivero et al.
2009
). Similarly, the c-tubulin
binding protein Cdk5RAP2 has been detected on both organelles and may have a
complementary role in microtubule nucleation (Wang et al.
2010
). There are
several other proteins, including myomegalin, Golgin-97, FTCD (58 K), and
CAP350 that associate with both organelles (Hagiwara et al.
2006
; Hoppeler-Lebel
et al.
2007
; Takatsuki et al.
2002
; Verde et al.
2001
), but the functional signifi-
cance of their specific localizations is not known.
Another example for a common function of the Golgi and the centrosome is
their role as signaling platforms. For instance, several proteins controlling cell
cycle progression have been detected at the centrosome. These include the kinase
complex Cdk1-Cyclin B, which is required for entry into mitosis (Jackman et al.
2003
) and centriolin, which controls cytokinesis and entry into S-phase (Gromley
et al.
2003
). In addition, signaling molecules, such as the protein kinases PKA and
NRD, proteasomal subunits, and cytoskeletal elements, such as actin and Arp2/3,
associate with the centrosome (Diviani et al.
2000
; Hubert et al.
2011
; Wigley
et al.
1999
). Similarly, Golgi membranes host a large number of signaling mole-
cules. For instance, components of the ras and src pathways have been detected on
the Golgi apparatus (Bard et al.
2002
; Chiu et al.
2002
; Wilson et al.
2011
). In
addition, cell cycle regulators, such as the mitotic cyclin B2 and the cytokinesis
regulator Nir2, localize to the Golgi (Jackman et al.
1995
; Litvak et al.
2004
). It is
clear that many of these Golgi- and centrosome-associated signaling molecules
fulfill functions that are unrelated to the primary roles of the Golgi or the cen-
trosome. Therefore, similar to the enrichment of membrane trafficking organelles
in the pericentrosomal region, it may be beneficial for a cell to place signaling
components in close proximity in its center.
A second association between the Golgi apparatus and the centrosome concerns
the regulatory crosstalk between these two organelles. For instance, there is a
signaling pathway by which the Golgi apparatus influences, and even controls, the
proper organization and function of the centrosome (Kodani and Sütterlin
2008
).
This pathway involves the cis Golgi protein GM130, which forms a complex with
the small GTPase Cdc42 and its specific guanine nucleotide exchange factor Tuba
at the Golgi (Kodani et al.
2009
; Kodani and Sütterlin
2008
). Interfering with
GM130, Tuba or Cdc42 causes the formation of a disorganized and non-functional
centrosome, suggesting that each of these three proteins is required for the
maintenance of normal centrosome morphology. It is not known at this point
whether additional signaling molecules are involved in this pathway, and how the
signal is transduced from one organelle to the other.
The mechanism(s) that support the functional interactions between the Golgi
and the centrosome are only beginning to be understood. As discussed above, cell
polarity appears to depend on the physical Golgi-centrosome proximity. However,
for other common functions, such as protein localization and signaling, the
