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

Abstract

The Ca2+-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 β-amyloid and in the regulation of the Ca2+ content in the endoplasmic reticulum. The role of DREAM in Ca2+ homeostasis was thus explored in SH-SY5Y cells stably or transiently overexpressing DREAM or a Ca2+-insensitive mutant of it. The overexpression of DREAM had transcriptional and posttranscriptional effects. Endoplasmic reticulum Ca2+ and capacitative Ca2+ influx were reduced in stably expressing cells. The previously shown down-regulation of Na+/Ca2+ exchanger 3 expression was confirmed; it could cause a local increase of subplasma membrane Ca2+ and thus inhibit capacitative Ca2+ influx. DREAM up-regulated the expression of the inositol 1,4,5-trisphosphate receptor and could thus increase the unstimulated release of Ca2+ through it. The transient coexpression of DREAM and presenilin potentiated the decrease of endoplasmic reticulum Ca2+ observed in presenilin-overexpressing cells. This could be due to a direct effect of DREAM on presenilin as the two proteins interacted in a Ca2+-independent fashion. © 2008 by The American Society for Biochemistry and Molecular Biology, Inc.