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Review
. 2014 Sep 5;369(1650):20130462.
doi: 10.1098/rstb.2013.0462.

The centrosome-Golgi apparatus nexus

Rosa M Rios  1
Affiliations
Review

The centrosome-Golgi apparatus nexus

Rosa M Rios. Philos Trans R Soc Lond B Biol Sci. .

Abstract

A shared feature among all microtubule (MT)-dependent processes is the requirement for MTs to be organized in arrays of defined geometry. At a fundamental level, this is achieved by precisely controlling the timing and localization of the nucleation events that give rise to new MTs. To this end, MT nucleation is restricted to specific subcellular sites called MT-organizing centres. The primary MT-organizing centre in proliferating animal cells is the centrosome. However, the discovery of MT nucleation capacity of the Golgi apparatus (GA) has substantially changed our understanding of MT network organization in interphase cells. Interestingly, MT nucleation at the Golgi apparently relies on multiprotein complexes, similar to those present at the centrosome, that assemble at the cis-face of the organelle. In this process, AKAP450 plays a central role, acting as a scaffold to recruit other centrosomal proteins important for MT generation. MT arrays derived from either the centrosome or the GA differ in their geometry, probably reflecting their different, yet complementary, functions. Here, I review our current understanding of the molecular mechanisms involved in MT nucleation at the GA and how Golgi- and centrosome-based MT arrays work in concert to ensure the formation of a pericentrosomal polarized continuous Golgi ribbon structure, a critical feature for cell polarity in mammalian cells. In addition, I comment on the important role of the Golgi-nucleated MTs in organizing specialized MT arrays that serve specific functions in terminally differentiated cells.

Keywords: AKAP450; Golgi apparatus; centrosome; microtubules.

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Figures

Figure 1.
Figure 1.
Subcellular localization of AKAP450, CDK5Rap2 and CAP350 by immunofluorescence analysis of interphasic RPE-1 epithelial cells (R. M. Rios 2010 & 2011, unpublished results). (a) Shows single labellings and (b) double immunofluorescence stainings of these proteins (as indicated). GMAP210 was included as a Golgi marker in the line at left. Arrows indicate the position of the centrosome. Scale bar, 10 μm.
Figure 2.
Figure 2.
The centrosome–GA nexus. (a,b) Similar multiprotein complexes are present at both the cis-face of the GA (a) and the PCM (b). These complexes contain AKAP450, CDK5Rap2, myomegalin and MT-anchoring proteins such as p150Glued. They are specifically recruited to the cis-GA through the interaction between GM130 and the N-terminal domain of AKAP450. Targeting to the centrosome is mediated by the AKAP450 C-terminal PACT domain. AKAP450 and CDK5Rap2 recruit γ-TuRCs and promote MT nucleation at both subcellular locations. Myomegalin and p150Glued might provide MT stabilization activities. (c) A working model for the mechanism of MT nucleation at the GA based on availaible data. During Golgi assembly, an MT nucleated by one multiprotein complex might be stabilized by another one located in the vicinity of the same or of a neighbouring stack, before being captured by TGN-associated CLASPs. This would facilitate the correct alignment of Golgi stacks preceding their fusion into a ribbon. MTs could stop growing at the TGN, thus generating an intra-GA network. Alternatively, they may continue to elongate towards the cell periphery. I propose that proteins such as AKAP450 or CDK5Rap2 represent not only functional but also physical connectors between the centrosome and the GA in mammalian cells.
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