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

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.