Table of Contents

Viewpoints

• • Isabelle M. Mansuy

  STEPping into Position: A New Player in the NMDA Receptor Game

  Mol Interv September 2002 2:282-284; doi:10.1124/mi.2.5.282
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  The posttranslational modification of proteins—phosphorylation or dephosphorylation of serine and threonine residues—is usually considered essential for the initiation and maintenance of long-term potentiation (LTP) and long-term depression (LTD) in neural plasticity. Pelkey et al. have identified at the N-methyl-d-aspartate (NMDA) receptor a protein tyrosine phosphatase—a member of the striatal-enriched phosphatase family, termed STEP₆₁—that appears to antagonize the effects of Src-mediated tyrosine phosphorylation during the facilitation of LTP. Mansuy reviews the findings of STEP₆₁ as a participant in modulating NMDA receptor-associated plasticity and discusses how differing populations of serine, threonine, and tyrosine phosphorylated or dephosphorylated residues might finely tune plasticity.

• • Stephen R. Cronin

  I’ll Simply Die Without My Calcium: Ca²⁺ Signaling and Surviving Cellular Stress

  Mol Interv September 2002 2:284-285; doi:10.1124/mi.2.5.284
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  Cunningham and colleagues have reported that the unfolded protein response (UPR) stimulates cellular influx of calcium, thereby activating calcium-dependent proteins such as calcineurin and calmodulin, and that this activation may be important for UPR. However, the authors have more importantly identified that the calcium signal is part of a larger pathway, termed the calcium cell survival (CCS) pathway, which is activated in response to several different types of stress. A key point is that the activation of the calcium-mediated events might lead to drug resistance in pathogenic fungi. Cronin examines these findings and discusses how the CCS might be subverted to render resistant fungi sensitive to treatment.

• • Erik Sahai

  p53 Moves Into Control of Cell Morphology

  Mol Interv September 2002 2:286-289; doi:10.1124/mi.2.5.286
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  Altered regulation of cell cycle, DNA repair, and apoptosis may not be the only ways that loss of p53 contributes to tumorigenesis. Roux and colleagues describe how the tumor suppressor protein p53 can regulate Cdc42-dependent (but neither RhoA- nor Rac-dependent) effects on cell morphology. The activation of p53 tends to inhibit the formation of Cdc42-dependent filopodia, pointing to a new way in which p53 exerts its tumor-suppressing activity: the prevention of cell spreading and motility. Sahai reviews these observations and discusses how insights gained from these studies will most likely lead to the identification of new targets for cancer therapy.

• • Tooraj Mirshahi and
  • Diomedes E. Logothetis

  GIRK Channel Trafficking: Different Paths for Different Family Members

  Mol Interv September 2002 2:289-291; doi:10.1124/mi.2.5.289
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  Ma et al. have reported that different G protein-regulated inwardly rectifying K⁺ (GIRK) channels composed of combinations of Kir3.1-Kir3.2-Kir3.3-Kir3.4 are localized to different subcellular compartments. Kir3.3 seems to target Kir3.1-containing channels to lysosomes, whereas Kir3.1-containing channels also consisting of Kir3.2 or Kir3.4 are successfully expressed at the cell surface. The new results suggest a mechanism whereby the surface expression of heterotetramers is controlled and thus channel density can be properly maintained. Mirshahi and Logothetis discuss the results and their implications for channel trafficking, but caution that we are far from understanding the whole regulatory process and that, indeed, other mechanisms participate in maintaining channel density.