Interplay of the Ca2+-binding protein DREAM with presenilin in neuronal Ca2+ signaling.

Abstract

The Ca(2+)-binding protein DREAM regulates gene transcription and Kv potassium channels in neurons but has also been claimed to interact with presenilins, which are involved in the generation of beta-amyloid and in the regulation of the Ca(2+) content in the endoplasmic reticulum. The role of DREAM in Ca(2+) homeostasis was thus explored in SH-SY5Y cells stably or transiently overexpressing DREAM or a Ca(2+)-insensitive mutant of it. The overexpression of DREAM had transcriptional and post-transcriptional effects. Endoplasmic reticulum Ca(2+) and capacitative Ca(2+) influx were reduced in stably expressing cells. The previously shown down-regulation of Na(+)/Ca(2+) exchanger 3 expression was confirmed; it could cause a local increase of subplasma membrane Ca(2+) and thus inhibit capacitative Ca(2+) influx. DREAM up-regulated the expression of the inositol 1,4,5-trisphosphate receptor and could thus increase the unstimulated release of Ca(2+) through it. The transient coexpression of DREAM and presenilin potentiated the decrease of endoplasmic reticulum Ca(2+) observed in presenilin-overexpressing cells. This could be due to a direct effect of DREAM on presenilin as the two proteins interacted in a Ca(2+)-independent fashion.