Trends in Cell Biology
OpinionCdc42 and Cellular Polarity: Emerging Roles at the Golgi
Section snippets
Cdc42 Acts Not Only at the Plasma Membrane But Also at the Golgi
Small GTPases play integral roles in intracellular signal transduction pathways. Thus, they are involved in the regulation of virtually all cellular processes 1, 2, 3, 4. Small GTPases typically act as molecular switches, cycling between the active (GTP bound) and the inactive (GDP bound) state. In their active state, these GTPases are typically localized to cellular membranes. Thus, a current concept has been that the compartmentalization of signaling molecules through membrane localization
The Golgi Pool Acts as a Reservoir for the Plasma Membrane Pool
The possibility that the Golgi pool of Cdc42 could serve as a reservoir for the pool at the plasma membrane was initially suggested by a yeast study that sought to examine how Cdc42 acts in polarity in the absence of external cues [12]. In this study, the targeted delivery of Cdc42 to a localized region of the plasma membrane was found to require the actin cytoskeleton and also a myosin motor [12]. Delivery of Cdc42 was also found to be dependent on the exocyst [12], which is a multimeric
The Golgi Pool Acts Independently of the Plasma Membrane Pool
The Golgi pool of Cdc42 can also act independently of its pool at the plasma membrane. In mammalian cells, the Golgi is formed by a series of flattened cisternae that can be subdivided into the cis, medial, and trans regions [18]. Early studies had suggested that transport within the Golgi stacks occurs through vesicles formed by the coat protein I (COPI) complex [19]. Subsequently, intra-Golgi transport was found to be more complex, with the movement of the Golgi stacks mediating anterograde
The Golgi Pool Acts in Conjunction with the Plasma Membrane Pool
Golgi-localized Cdc42 can also act by coordinating its function with the pool at the plasma membrane for complex events of cellular polarity. One such role involves Cdc42 controlling the positioning of the Golgi. In directed cell migration, it is well known that the Golgi polarizes toward the direction of cell movement and that altering this polarization impairs cell migration 27, 28. This role of Cdc42 has been found to be dependent on microtubules and also under the control of ARHGAP21, a
Concluding Remarks
We have highlighted above three general ways that the Golgi pool of Cdc42 can act (summarized in Figure 1). It appears that the Golgi-localized Cdc42 enables the cell to diversify the function of this small GTPase, which in some cases represents new roles and in other cases acts to complement its established roles at the plasma membrane. The elucidation of how Cdc42 acts at the Golgi also suggests key issues for further clarification in the future (see Outstanding Questions).
First, whether
Acknowledgments
Work in the Farhan laboratory is funded by the Swiss National Science Foundation, the German Science Foundation, the Young Scholar Fund of the University of Konstanz, and the Biotechnology Institute Thurgau. Work in the Hsu laboratory is funded by the National Institutes of Health (GM058615).
References (45)
Signaling interplay in Ras superfamily function
Curr. Biol.
(2005)Ras/MAPK signaling from endomembranes
Mol. Oncol.
(2009)GEFs and GAPs: critical elements in the control of small G proteins
Cell
(2007)Mammalian Cdc42 is a brefeldin A-sensitive component of the Golgi apparatus
J. Biol. Chem.
(1996)- et al.
Passage through the Golgi
Curr. Opin. Cell Biol.
(2010) Characterization of the association of the actin-binding protein, IQGAP, and activated Cdc42 with Golgi membranes
J. Biol. Chem.
(1998)Tuba, a novel protein containing bin/amphiphysin/Rvs and Dbl homology domains, links dynamin to regulation of the actin cytoskeleton
J. Biol. Chem.
(2003)PTEN-mediated apical segregation of phosphoinositides controls epithelial morphogenesis through Cdc42
Cell
(2007)Rac1 and Cdc42 capture microtubules through IQGAP1 and Clip-170
Cell
(2002)Human RAS superfamily proteins and related GTPases
Sci. STKE
(2004)
The Ras superfamily at a glance
J. Cell Sci.
Signalling to and from the secretory pathway
J. Cell Sci.
Mammalian Rho GTPases: new insights into their functions from in vivo studies
Nat. Rev. Mol. Cell Biol.
Cdc42 – the centre of polarity
J. Cell Sci.
Differential localization of Rho GTPases in live cells: regulation by hypervariable regions and RhoGDI binding
J. Cell Biol.
Activation of endogenous Cdc42 visualized in living cells
Science
Spontaneous cell polarization through actomyosin-based delivery of the Cdc42 GTPase
Science
Tethering factors as organizers of intracellular vesicular traffic
Annu. Rev. Cell Dev. Biol.
Spatial control of Cdc42 signalling by a GM130–RasGRF complex regulates polarity and tumorigenesis
Nat. Commun.
Cdc42 localization and cell polarity depend on membrane traffic
J. Cell Biol.
ARF family G proteins and their regulators: roles in membrane transport, development and disease
Nat. Rev. Mol. Cell Biol.
Recycling endosomes can serve as intermediates during transport from the Golgi to the plasma membrane of MDCK cells
J. Cell Biol.
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