Double Duty for an Essential Subunit of Eukaryotic Translation Initiation Factor 2B
Translation is downregulated during starvation or stress by phosphorylation of eukaryotic translation initiation factor 2 (eIF2) and attendant inhibition of its complicated, multisubunit guanine nucleotide exchange factor (GEF) eIF2B. Only one of the five subunits is sufficient for GEF activity in vitro, posing the question of why three other eIF2B subunits are essential in vivo. Dev et al. (p. 5218-5233) provide compelling evidence that the β subunit is crucial for efficient binding of the unphosphorylated substrate (eIF2-GDP) in a manner conducive to nucleotide exchange, in addition to its role in mediating a distinct, nonproductive mode of binding to phosphorylated eIF2 that impedes GEF function.
Location, Location, Location: the Pattern of Cell Surface Localization Is Critical to the Function of Two Rho GTPases
Localization of Rho GTPases is thought to be an important determinant of their function within the cell. In Saccharomyces cerevisiae a polarized patch of Cdc42 on the cell surface is critical to promoting polarized growth during the early stages of bud emergence. Rho3, however, is required at a later stage, when growth entails a more uniform “isotropic” expansion of the bud. Work by Wu and Brennwald (p. 5207-5217) explores the role of localization of these Rho GTPases in their distinct functions. They find Rho3 in a dispersed pattern on the plasma membrane that is linked to its role in isotropic growth of the bud. A small region in Rho3 that is critical for its localization is identified. Remarkably, addition of this region to Cdc42 gives rise to protein that both localizes and functions as Rho3, demonstrating a strong connection between localization and function for these GTPases.
Role of Phospholipase D2 Phosphorylation by Protein Kinase Cδ in Spreading of Cells
Integrin signaling plays critical roles in cell adhesion, spreading, and migration, and localized actin remodeling is required to regulate these functions. Chae et al. (p. 5086-5098) found that integrin-dependent phospholiapase D2 (PLD2) phosphorylation by protein kinase C (PKCδ) is essential for PLD targeting to membrane ruffles to trigger Rac translocation and lamellipodium formation during cell spreading. These findings suggest a bridge between PKCδ activation and actin cytoskeletal rearrangement in the integrin signaling pathway via PLD activation and provide a novel molecular mechanism for localized PLD activation for cell spreading.
- Copyright © 2010 American Society for Microbiology
