Cdc42: An Essential Rho-Type GTPase Controlling Eukaryotic Cell Polarity

Abstract

SUMMARY Cdc42p is an essential GTPase that belongs to the Rho/Rac subfamily of Ras-like GTPases. These proteins act as molecular switches by responding to exogenous and/or endogenous signals and relaying those signals to activate downstream components of a biological pathway. The 11 current members ofthe Cdc42p family display between 75 and 100% amino acid identity and are functional as well as structural homologs. Cdc42p transduces signals to the actin cytoskeleton to initiate and maintain polarized gorwth and to mitogen-activated protein morphogenesis. In the budding yeast Saccharomyces cerevisiae, Cdc42p plays an important role in multiple actin-dependent morphogenetic events such as bud emergence, mating-projection formation, and pseudohyphal growth. In mammalian cells, Cdc42p regulates a variety of actin-dependent events and induces the JNK/SAPK protein kinase cascade, which leads to the activation of transcription factors within the nucleus. Cdc42p mediates these processes through interactions with a myriad of downstream effectors, whose number and regulation we are just starting to understand. In addition, Cdc42p has been implicated in a number of human diseases through interactions with its regulators and downstream effectors. While much is known about Cdc42p sturcture and functional interactions, little is known about the mechanism(s) by which it transduces signals within the cell. Future research sould focus on this question as well as on the detailed analysis of the interactions of Cdc42p with its regulators and downstream effectors.

Functional characterization of the Bag7, Lrg1 and Rgd2 RhoGAP proteins from Saccharomyces cerevisiae

“…Moreover, it has been shown that Bag7p overproduction suppresses the cold sensitivity of a sac7 strain [13]. The Lrg1 protein seems to play a role during the mating process in yeast [34], and Cdc42p has also been shown to act during mating projection formation [35]; these data indicate that the interaction between Lrg1p and Cdc42p is signi¢cant. Rgd2p interacts with the Cdc42p and Rho5p.…”

Adaptor functions of Cdc42, Ste50, and Sho1 in the yeast osmoregulatory HOG MAPK pathway

“…The Ile-46 to Met (I46M) substitution in Cdc42 inhibits the binding between Cdc42 and the Ste50 RA domain, and cdc42-I46M mutant cells are defective in the FG response (Mösch et al, 2001;Truckses et al, 2006). The positions of Leu-4 and Ile-46 are far from the GTP binding/hydrolysis domains and the effector binding regions called Switch I (residues 26-40) and Switch II (residues 58-76) (Johnson, 1999). It is therefore likely that Cdc42 binds to the Ste50 RA domain and to the Ste20/Cla4 CRIB domain via different regions of the molecule.…”

Gene expression profiles in rat intestine identify pathways for 1,25-dihydroxyvitamin D3 stimulated calcium absorption and clarify its immunomodulatory properties

“…cells, Cdc42 has been implicated in the regulation of an actin rearrangement, receptor-mediated signal transduction pathways, cell cycle progression, apoptosis and multiple membrane trafficking events, including phagocytosis, exocytosis, and endocytosis. Cdc42 may also govern pathways required for establishment and maintenance of cellular polarity [49]. Expression of skeletal muscle a-actin (a-SMA) and thymosin b-10 (TB-10)-the intracellular matrix related genes-was strongly inhibited at 6 h by 1,25-(OH) 2 D 3 ( Table 4).…”