Actin polymerization nucleation

Condeelis, J. 2001. How is actin polymerization nucleated in vivo Trends Cell Biol. 11 288-93. 

The Locomotion of Amoeba The Locomotion of Fibroblastic Cell Types The Locomotion of Leukocytes The Behavior of Locomoting Cells The Role of the Cytoskeleton in Cell Locomotion The Microtubule-Based Cytoskeleton The Intermediate Filament-Based Cytoskeleton The Microfilament-Based Cytoskeleton The Organization of Microfilaments in Cells Microfilament Dynamics and Cell Locomotion Sites of Lamellar Protrusion May Be Determined by the Nucleation of Actin Polymerization... 

Sites of Lamellar Protrusion May Be Determined by the Nucleation of Actin Polymerization... 

Fig. 1. Toxin-catalyzed ADP-ribosylation inhibits nucleation activity of the gelsolin-octin complex. In the presence of Ca, gelsotin forms a 1 1 and a 1 2 complex with octin monomers at the so-called EGTA-resistant (a) and Ca -sensitive (b) binding site, respectively. Gelsolin-actin complexes act as nuclei for actin polymerization. Actin bound to both sites (a, b) can be ADP-ribosylated. Whereas ADP-ribosylation of actin bound to the EGTA-resistant site has no effect on nucleation, ADP-ribosylation of actin bound to the Ca " -sensitive site inhibits nucleation activity of the gelsolin-actin complex...

The rate-limiting step in actin polymerization appears to be nucleation, the formation of an actin cluster large enough (typically three or four G-actins) for the rate of monomer association to exceed the rate of dissociation. Once filaments of this size form, they continue to grow, and the concentration of G-actin monomers decreases until it is in equilibrium with F-actin. The concentration of monomeric actin at equilibrium is called the critical concentration, Cc. In vitro, Cc is 0.1 mM. The value in vivo is variable, depending in part on the concentration of ATP. In the presence of ADP, instead of ATP, both ends of the filament grow at the characteristic slow rate. ATP speeds up the rate of polymerization and lowers the effective Cc. 

The assembly of microtubules bears certain similarities to that of actin, but GTP is required rather than ATP. The OC-/1 dimers bind GTP and then associate to form oligomers. These oligomers form nucleation sites for the growth of microtubules (Figure 8.20). One end, called the plus end, grows more rapidly than the other, minus end. As in actin polymerization, the nucleotide is hydrolyzed but is held in the filament. The final assembly of a functional microtubule usually involves the binding of other proteins to its surface. 

Zhao W, Jiang C, Kroll TT, Huber PW (2001) A proline-rich protein binds to the localization element of Xenopus Vgl mRNA and to Ugands involved in actin polymerization. EMBO J 20 2315-2325 Zhou F, Leder P, Martin SS (2006) Formin-1 protein associates with microtubules through a peptide domain encoded by exon-2. Exp Cell Res 312 1119—1126 Zigmond SH (2004) Formin-induced nucleation of actin filaments. Curr Opin Cell Biol 16 99—105... 

Sanders, M.C., Wang, Y.L. (1990). Exogenous nucleation sites fail to induce detectable polymerization of actin in living cells. J. Cell Biol. 110,359-365. 

---