Table of Contents

February 2003; 3 (1)

Speaking of Pharmacology



  • In addition to their well-studied ability to transactivate the expression of many genes, estrogen receptors (ERs) also effect cytoplasmic changes occurring too quickly to be accounted for by gene expression. Indeed, these immediate, “nongenomic” effects have been intensely studied, but the identification of important protein partners in quick ER-mediated signaling has lagged behind. Now, Wong et al. have identified MNAR (modulator of nongenomic activity of estrogen receptor) as an adaptor protein that allows the ER to bridge the signaling pathways of tyrosine kinases (i.e., Src) and the mitogen-activated protein kinase (MAPK) cascade. The MNAR–ER complex also appears to positively influence ER-mediated gene expression.

  • Brief periods of repetitive neural firing onto adjacent neurons can lead to changes in synaptic plasticity, that is, changes in the make-up of macromolecular complexes located at synapses. This process includes the regulated trafficking of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) to synaptic membranes. Little is known, however, about how the AMPARs are regulated before they are shuttled to the membrane. Greger et al. have found that the length of the cytoplasmic tails of constituent subunits of a given AMPAR is determined by editing [at a glutamine (Q) or an arginine (R) codon] near their C termini. Tail length, in turn, dictates whether AMPARs will be retained or quickly released from the endoplasmic reticulum.


  • The intrinsic, or intracellular and mitochondria-mediated, pathway of apoptosis requires the formation of a large macromolecular structure termed the apoptosome, which comprises cytochrome c (released from mitochondria), proteolytic enzymes called caspases, Apaf-1, as well as other unidentified proteins. Structural details of the apoptosome have recently emerged, which could lead to exploiting its activation or deactivation in tumors or in some instances of tissue degeneration, respectively.

  • Schizophrenia strikes one percent of the population worldwide, irrespective of race, geography, culture, or economic status. The disease generally compromises the reproductive success of afflicted individuals, and so its steady rate of occurrence, at least since it was first described around the beginning of the twentieth century, is intriguing. The complexity of its genetic basis certainly explains, at least in part, why the disorder has not disappeared from the gene pool. The continued presence of the disease, more obviously, reflects the difficulty of finding effective therapy. This difficulty may ultimately be circumvented, however, as more is learned about the specific genetic alleles, environmental influences, and neurodevelopmental programs that conspire to yield what was originally referred to as the “fragmented mind.”

Beyond the Bench

Net Results