cdc42 regulates the exit of apical and basolateral proteins from the trans-Golgi network

Abstract

It is well established that Rho-GTPases regulate vesicle fusion and fission events at the plasma membrane through their modulatory role on the cortical actin cytoskeleton. In contrast, their effects on intracellular transport processes and actin pools are less clear. It was recently shown that cdc42 associates with the Golgi apparatus in an ARF-dependent manner, similarly to coat proteins involved in vesicle formation and to several actin-binding proteins. We report here that mutants of cdc42 inhibited the exit of basolateral proteins from the trans-Golgi network (TGN), while stimulating the exit of an apical marker, in two different transport assays. This regulation may result from modulation of the actin cytoskeleton, as GTPase-deficient cdc42 depleted a perinuclear actin pool that rapidly exchanges with exogenous fluorescent actin.

Regulation of actin cytoskeleton dynamics by Arf-family GTPases

“…Cdc42 also associates strongly with Golgi membranes, where it regulates both retrograde transport from the Golgi to the ER [14] and exit from the trans-Golgi network (TGN) [15]. Early studies revealed that association of Cdc42 with the Golgi was sensitive to BFA, suggesting that Arf activation was necessary for Cdc42 recruitment [16].…”

The epithelial polarity program: machineries involved and their hijacking by cancer

“…Downregulation of Cdc42 or expression of dominant negative mutants of Cdc42 results in aberrant lumen formation and accumulation of intracellular lumens or VACs (Martin-Belmonte et al, 2007) described earlier in the review (Figure 3b). Cdc42 also has important functions in polarized trafficking from the Golgi complex; it regulates differently the exit of apical and basolateral proteins from the TGN (Kroschewski et al, 1999;Cohen et al, 2001;Musch et al, 2001), presumably by organizing the local actin cytoskeleton at the perinuclear region (Kroschewski et al, 1999;Cohen et al, 2001;Musch et al, 2001) and through interactions with the exocyst Yeaman et al, 2004b) (Figures 1 and 3a).…”

Faciogenital Dysplasia Protein (FGD1) Regulates Export of Cargo Proteins from the Golgi Complex via Cdc42 Activation

“…Importantly, the main FGD1 target, Cdc42, has a fundamental role in the coordination of membrane transport events, via reorganization of the cytoskeleton and other signaling events (Erickson and Cerione, 2001). In this way, Cdc42 coordinates various aspects of membrane transport, including kinetics (Musch et al, 2001) and fidelity (Kroschewski et al, 1999;Musch et al, 2001) of post-Golgi transport and protein targeting to different surface domains in polarized cells (Kroschewski et al, 1999;Musch et al, 2001).…”