Cytoskeleton 118-124 PDF

The dramatic effects of Cdc42, Rac, and Rho on actin organization in fibroblasts. In each case, the actin filaments have been labeled with fluorescent phalloidin. (A) Serum-starved fibroblasts have actin filaments primarily in the cortex and relatively few stress fibers. (B) Microinjection of a con...

The dramatic effects of Cdc42, Rac, and Rho on actin organization in fibroblasts. In each case, the actin filaments have been labeled with fluorescent phalloidin. (A) Serum-starved fibroblasts have actin filaments primarily in the cortex and relatively few stress fibers. (B) Microinjection of a constitutively activated form of Cdc42 results in many long filopodia at the cell periphery. (C) Microinjection of a constitutively activated form of Rac causes the formation of an enormous lamellipodium that extends from the entire circumference of the cell. (D) Microinjection of a constitutively activated form of Rho causes the rapid assembly of many prominent stress fibers. Cdc42 establishes yeast-cell polarity. (A) A positive feedback loop by which Cdc42-GTP recruits its own GEF to the plasma membrane to generate a focal site of Cdc42 activity. (B) Local activation of a formin protein by Cdc42-GTP nucleates actin filament assembly. Transport of vesicles along these actin filaments toward their plus ends by myosin V delivers cargoes necessary for growth of the bud. PAR proteins establish two distinct cortical domains in C. elegans. (A) Symmetry breaking and polarity establishment occur in the fertilized egg before the maternal and paternal nuclei meet. After sperm entry, its centrosome duplicates and nucleates microtubules that decrease Rho GEF activity at what will become the posterior end of the embryo. This leads to accumulation of the anterior PAR proteins (including Par-3), allowing posterior PAR proteins (including Par-2) to bind the cortex at the posterior end. (B) Prior to fertilization, bundles of fluorescently labeled myosin II (white) are distributed throughout the cortex of the unpolarized egg because of the uniform distribution of activated Rho all along the plasma membrane, resulting in uniform cortical acto- myosin contractility. (C) After fertilization, local depletion of the Rho GEF near the sperm entry site (at right in this image) reduces myosin levels and contractility in the posterior cortex of the cell. (D) Par complex localization after polarization with Par-3 (red) at the anterior and Par-2 (green) at the posterior of the zygote. Multiple mechanisms operate to maintain this asymmetry through mutual antagonism between anterior and posterior PAR proteins Cell-polarity protein modules identified in Drosophila. (A) PAR and Crumbs proteins cooperate to assemble the apical domain and junctional complexes, whereas Scribble defines the basolateral domain. Scribble and PAR are mutually antagonistic, whereas PAR and Crumbs reinforce each other. Cdc42 helps to recruit PAR proteins. The contrasting effects of Rac and Rho activation on actin organization. (A) Activation of the small GTPase Rac leads to alterations in actin accessory proteins that promote the formation of protrusive actin networks in lamellipodia and pseudopodia. (B) Activation of the related GTPase Rho leads to nucleation of actin filaments by formins and increases contraction by myosin II, promoting the formation of contractile actin bundles at the rear of the cell and assembly of stress fibers. myosin heavy chain (MHC) myosin light-chain kinase (MLCK) Neutrophil polarization and chemotaxis. (B) Binding of bacterial molecules to G-protein- coupled receptors on the neutrophil stimulates directed motility. These receptors are found all over the surface of the cell, but are more likely to be bound to the bacterial ligand at the front. Two polarization. At the front of the cell, stimulation of the Rac pathway leads, via the trimeric G protein Gi, to growth of protrusive actin networks. Second messengers within this pathway are short-lived, so protrusion is limited to the region of the cell closest to the stimulant. The same receptor also stimulates a second signaling pathway, via the trimeric G proteins G12 and G13, that triggers the activation of Rho. The two pathways are mutually antagonistic. Because Rac-based protrusion is active at the front of the cell, Rho is activated only at the rear of the cell, stimulating contraction of the cell rear and assisting directed movement.