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First published online March 12, 2004
doi: 10.1242/10.1242/jcs.01115

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Cdc42 - the centre of polarity

CNRS-UMR144-Institut Curie, 26 rue d'Ulm, 75248 Paris CEDEX 05, France

View larger version (26K): [in a new window]   Fig. 1. Cdc42 during budding yeast polarization. Budding yeast can polarize in response to two main stimuli: they undergo polarized growth, which leads to budding, and they respond to pheromone gradient during mating by forming a shmoo. These stimuli both lead to Cdc42 recruitment and activation at the site of polarized growth through distinct signalling cascades (pink). Far1p associates with the Cdc42p-GEF Cdc24p and plays a key role in Cdc42p activation. During budding, Far1p degradation allows Cdc24p exit form the nucleus and, during mating, it binds Gß and thereby recruits Cdc24p to the site of polarization. The active, GTP-bound form of Cdc42p (green) regulates multiple direct (solid line) or indirect (dashed line) effectors (blue), which control several cell functions. The co-ordinate polarization of septins, actin and microtubule structures, and of membrane trafficking, allows a polarized growth that leads during budding to the formation of a bud and during mating to the formation of a shmoo.

View larger version (16K): [in a new window]   Fig. 2. Multiple pathways controlling Cdc42 activation. In multicellular organisms, cells respond to a wide range of external signals that promote cell polarization (chemotactic signals, physical stress, cell-cell contacts). These signals are transduced by different families of receptors (purple) that can all regulate Cdc42. The signalling pathways involve several intermediates (pink) that eventually recruit and activate a Cdc42-GEF. Although some of the GEFs have been identified, the precise mechanisms involved are still to be determined.

View larger version (17K): [in a new window]   Fig. 4. Multiple signalling pathways controlled by Cdc42. Cell polarization requires the spatial and temporal regulation of several cell components. Orientation of the actin and microtubule cytoskeletons, regulation of cell contacts and organization of membrane traffic occur in concert. Multiple signalling pathways downstream of Cdc42 regulate these different cellular components (black box). These signals are transduced by different Cdc42 direct (solid line) or indirect (dotted line) effectors (blue) and involve several intermediates (blue). Cell polarization results from the localized activation of Cdc42, which leads to a localized regulation of cellular components and therefore to their asymmetric organization. The different cellular components cooperate and generate the general characteristics of cell polarization.

View larger version (34K): [in a new window]   Fig. 3. Cellular functions regulated by Cdc42 in different polarized cell types. Most cell types can polarize under certain circumstances. This figure presents a few examples of polarized cells to highlight the multiplicity of aspects of cell polarity. Cell polarization results from the coordinate regulation of several cell functions. Most of these functions are under the control of Cdc42. (A) In migrating fibroblasts, the actin cytoskeleton promotes extension of the leading edge and retraction of the rear of the cell, the microtubule system associated with the centrosome aligns along the direction of migration and the Golgi apparatus faces the front of the cell and vesicular trafficking is oriented towards the leading edge. (B) During contact with a target cell, a cytotoxic T cell presents a polarized organization that allows the formation of a strong and stable cell-cell contact, and the orientation of the microtubule cytoskeleton and the secretory pathway in the direction of this contact. (C) In differentiated epithelial cells, the entire cell organization is polarized and allows the segregation of apical and baso-lateral proteins and membrane domains separated by tight junctions. The intracellular organization is also characterized by polarized cytoskeletal structures and polarized membrane traffic. (D) In the C. elegans zygote, the first division is asymmetric. The microtubule system is polarized, with asymmetric forces exerted on each pole of the embryo. This leads to an asymmetric positioning of the mitotic spindle. The protein distribution in the cytoplasm is also polarized, which will give rise to two non-equivalent daughter cells.

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