Reading networks at rest.

Resting-state functional connectivity (RSFC) approaches offer a novel tool to delineate distinct functional networks in the brain. In the present functional magnetic resonance imaging (fMRI) study, we elucidated patterns of RSFC associated with 6 regions of interest selected primarily from a meta-analysis on word reading (Bolger DJ, Perfetti CA, Schneider W. 2005. Cross-cultural effect on the brain revisited: universal structures plus writing system variation. Hum Brain Mapp. 25: 92-104). In 25 native adult readers of English, patterns of positive RSFC were consistent with patterns of task-based activity and functional connectivity associated with word reading. Moreover, conjunction analyses highlighted the posterior left inferior frontal gyrus and the posterior left middle temporal gyrus (post-LMTG) as potentially important loci of functional interaction among 5 of the 6 reading networks. The significance of the post-LMTG has typically been unappreciated in task-based studies on unimpaired readers but is frequently reported to be a locus of hypoactivity in dyslexic readers and exhibits intervention-induced changes of activity in dyslexic children. Finally, patterns of negative RSFC included not only regions of the so-called default mode network but also regions involved in effortful controlled processes, which may not be required once reading becomes automatized. In conclusion, the current study supports the utility of resting-state fMRI for investigating reading networks and has direct relevance for the understanding of reading disorders such as dyslexia.

Characterization of an aldolase-binding site in the Wiskott-Aldrich syndrome protein.

The thrombospondin-related anonymous protein (TRAP) is an essential transmembrane molecule in Plasmodium sporozoites. TRAP displays adhesive motifs on the extracellular portion, whereas its cytoplasmic tail connects to actin via aldolase, thus driving parasite motility and host cell invasion. The minimal requirements for the TRAP binding to aldolase were scanned here and found to be shared by different human proteins, including the Wiskott-Aldrich syndrome protein (WASp) family members. In vitro and in vivo binding of WASp members to aldolase was characterized by biochemical, deletion mapping, mutagenesis, and co-immunoprecipitation studies. As in the case of TRAP, the binding of WASp to aldolase is competitively inhibited by the enzyme substrate/products. Furthermore, TRAP and WASp, but not other unrelated aldolase binders, compete for the binding to the enzyme in vitro. Together, our results define a conserved aldolase binding motif in the WASp family members and suggest that aldolase modulates the motility and actin dynamics of mammalian cells. These findings along with the presence of similar aldolase binding motifs in additional human proteins, some of which indeed interact with aldolase in pull-down assays, suggest supplementary, non-glycolytic roles for this enzyme.