In previous work, we showed that peptides from endocytosed proteins containing the tyrosine YXXphi sorting motif are recognized by the mu 2 subunit of AP-2, the plasma membrane clathrin adaptor protein complex. This interaction is activated by phosphoinositide lipids that are phosphorylated at the D-3 position of the inositol ring, and is also enhanced by the formation of clathrin-AP-2 coats. H...

The largest superfamily of membrane proteins that translate extracellular signals into intracellular messages are the 7-transmembrane-spanning (7TM) G protein-coupled receptors (GPCR). One of the ways in which their activity is controlled is by the process of desensitization and endocytosis, whereby agonist-activated receptors are rapidly and often reversibly silenced through removal from the c...

To investigate mechanisms of apical sorting in the secretory pathway of epithelial cells, we expressed varying amounts of the 165 amino acid isoform of vascular endothelial growth factor (VEGF(165)) and transforming growth factor beta1 (TGF-beta1) via replication defective adenoviruses. Apical sorting of both proteins was efficient at low expression levels but saturated or was reversed at high ...

Activated EGF (epidermal growth factor) receptors are removed from the cell surface via endocytosis and subsequent degradation in the lysosome. This ultimately attenuates EGF receptor signals and diminishes the level of cell activation. The mechanisms underlying the EGF receptor down-regulation are beginning to be elucidated at the molecular level. Recent reports have indicated that receptor mo...

Polarized cells such as epithelial cells and neurons exhibit different plasma membrane domains with distinct protein compositions. Recent studies have shown that sorting of transmembrane proteins to the basolateral domain of epithelial cells and the somatodendritic domain of neurons is mediated by recognition of signals in the cytosolic domains of the proteins by adaptors. These adaptors are co...

Proteins migrate from the site of their synthesis to intracellular, surface, or extracellular sites depending on their function. This well-illustrated overview provides an introduction to the pathways of protein trafficking. It includes descriptions of the relevant cellular compartments, modifications associated with the movement of proteins through these compartments, signals used for targetin...

Children's mathematical skills were considered in relation to executive functions. Using multiple measures--including the Wisconsin Card Sorting Task (WCST), dual-task performance, Stroop task, and counting span-it was found that mathematical ability was significantly correlated with all measures of executive functioning, with the exception of dual-task performance. Furthermore, regression anal...

Stroke is difficult to treat with few treatment options. Until such time as appropriate therapeutic regimens are established, prevention, both in the primary and in the secondary setting, is of paramount importance. Evaluation of pharmacological agents for the prevention of stroke in conventional clinical studies has the advantage that the outcome parameter is a direct measure of efficacy, and ...