School of Life Sciences

Neuregulin-1 signaling molecules have various roles in the nervous system, including effects on neuronal migration and differentiation. In mouse cerebellar granule neurons the effects of neuregulin-1 (type I) are mediated by a homo-dimeric ErbB4 receptor, which can interact with the PSD-95 protein through a C-terminal motif. To determine whether this interaction is critical for signaling we introduced into granule cells a decoy peptide representing the C-terminal 20 amino acids of the mouse ErbB4 receptor. Exposure of unloaded cells to neuregulin-1 did not alter neurite density but increased average neurite length by 50%. In contrast, granule cell cultures loaded with the decoy peptide were unresponsive to the ligand. We conclude that the association of ErbB4 with PSD-95 is important for neuregulin-induced neuronal differentiation.

The high-performance liquid chromatography (HPLC) method employing stationary phases immobilized with plasma proteins was used for this study to investigate the structural properties governing drug-plasma protein binding. A set of 65 compounds with a broad range of structural diversity (in terms of volume, hydrogen-bonding, polarity and electrostatic force) were selected for this purpose. The Abraham linear free energy relationship (LFER) analyses of the retention factors on the immobilized HSA (human serum albumin) and AGP (α1-acid glycoprotein) stationary phases showed that McGowan's characteristic molecular volume (V), dipolarity/polarizability (S) and hydrogen bond basicity (B) are the three significant molecular descriptors of solutes determining the interaction with immobilized plasma proteins, whereas excess molar refraction (E) is less important and hydrogen bond acidity (A) is not of statistical significance in both systems, for electrically neutral compounds. It was sh...