Interplay of the Ca2+-binding Protein DREAM with Presenilin in Neuronal Ca2+ Signaling

Laura Fedrizzi,Dmitry Lim,Ernesto Carafoli,Marisa Brini

doi:10.1074/jbc.m804152200

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.

Highlights

Few reports have explored the possible roles of DREAM in the regulation of neuronal Ca2ϩ signals
The precise control of Ca2ϩ homeostasis and, of Ca2ϩ quantified by densitometric Western blotting analysis and signaling is essential for neuronal development and function; found to be the same in SH-SY5Y cells transfected with PS2 abnormalities in the signaling operation are commonly alone or co-transfected with PS2 and DREAM plasmids (data involved in the origin of neurodegenerative disorders [33, 34]. not shown)
The results showed that endoplasmic reticulum (ER) Ca2ϩ was not modified Ca2ϩ homeostasis and, Ca2ϩ signaling require the conby the transient expression of wild type (WT) and EFmDREAM, suggest- certed action of specific transport systems in the plasma mem

Summary

Introduction

Few reports have explored the possible roles of DREAM in the regulation of neuronal Ca2ϩ signals. The increase of cytosolic Ca2ϩ due to the enhanced Ca2ϩ leak from the ER was the same in control cells, in the WT DREAM, and in EFmDREAM clones (Fig. 2B).

Results

Conclusion