Several presentations focused on the role of presenilins in calcium signaling pathways. Leissring and LaFerla (Abstract 474.7) reported that cells from mutant PS1 knockin mice are deficient in capacitative calcium entry (i.e., the influx of calcium triggered by depletion of intracellular calcium stores), a finding they recently reported in J Cell Biol;149: 793-798. Intriguingly, Kim, Tanzi, and colleagues (abstract 474.9) found that inhibitors of capacitative calcium entry lead to increased β-amyloid production, suggesting that this signaling pathway may regulate presenilin-mediated γ-secretase activity. In support of this regulatory link, Leissring et al. found that a tight correlation exists between the relative amount of β-secretase activity in PS1 and PS2 knockout cells and their sensitivity to agonists that stimulate release of intracellular calcium. LaFerla’s group provided evidence that presenilin mutations alter intracellular calcium levels, leading to increased calcium in the endoplasmic reticulum. This finding was nicely complemented in a nearby poster by Yang and Cook (Abstract 474.8) showing that intracellular calcium stores are, conversely, decreased in neurons from PS1 knockout animals. Finally, Sisodia (Abstract 298.5) showed evidence that a region of the presenilin molecule is homologous to potassium channels, raising tantalizing new questions about the role of presenilins in ion homeostasis. Clearly, interest in the role of presenilins in ion signaling is gaining momentum, and several interesting stories are bound to emerge in this area in the near future.-Brian J Cummings.
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