Breaking down Arp2/3 function

Heat shock gene resides in a pore neighborhood R ohner et al. describe how the heat shock gene hsp-16.2 associates with nuclear pore complexes in C. elegans cells. Genes can occupy specifi c positions within the nucleus, and their localization may change upon activation or repression. Developmentally regulated genes in C. elegans, for example, move from the periphery to the interior of nuclei in response to gene induction. In contrast, Rohner et al. found that the worm stress response gene hsp-16.2 tended to localize near the nuclear envelope in its inactive state and became even more enriched at the nuclear periphery when induced by heat shock. Transgenes containing the minimal hsp-16.2 promoter showed similar localization patterns, indicating that the promoter region, rather than any other sequences or the gene's chromosomal location, controls hsp-16.2 positioning. Using super-resolution microscopy and chromatin immunoprecipitation, the researchers found that the promoter localized near nuclear pore complexes before gene induction and then increased its association with the pores upon heat shock. hsp-16.2's association with nuclear pores was mediated by several factors that bind to the gene's promoter. Knocking down heat shock transcription factor 1 or expressing heat-sensitive mutants of RNA polymerase II abolished the gene's peripheral localization. hsp-16.2 positioning also required the polymerase-associated protein ENY-2, which binds to nuclear pores and promotes mRNA processing and export. hsp-16.2's peripheral local-ization may therefore speed up heat shock protein production in times of stress. But senior author Susan Gasser thinks that, in the uninduced state, pore-associated factors might help limit gene expression by promoting mRNA turnover. A TP hydrolysis by the Arp2/3 complex promotes the disassem-bly of lamellipodial actin networks , Ingerman et al. reveal. The Arp2/3 complex generates branched actin networks and lamellipodial cell protrusions by nucleating new actin fi laments from the sides of preexisting ones. The complex contains two actin-related proteins, Arp2 and Arp3, that bind ATP in a conserved nucleotide-binding pocket, like actin itself. ATP hydrolysis by actin destabilizes polymerized actin fi laments, but the effect of ATP hydrolysis by Arp2 and Arp3 remains unclear. Ingerman et al. made hydrolysis-defective versions of Arp2 and Arp3. These mutants were still able to nucleate actin fi laments and support the assembly of branched actin networks in cells. But hydrolysis-defective Arp2/3 complexes took longer to dissociate from actin fi laments, thereby delaying—but not preventing—net-work turnover. Complexes containing mutant versions of both Arp2 and Arp3 were even slower to …