Interplay of the Ca2+-binding protein DREAM with presenilin in neuronal Ca2+ signaling.
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.
Fedrizzi
Laura
L
Biochemistry, University of Padova, Padova 35131, Italy; Experimental Veterinary Sciences, University of Padova, Padova 35131, Italy.
Lim
Dmitry
D
Biochemistry, University of Padova, Padova 35131, Italy; Venetian Institute of Molecular Medicine, Padova 35129, Italy.
Carafoli
Ernesto
E
Biochemistry, University of Padova, Padova 35131, Italy; Venetian Institute of Molecular Medicine, Padova 35129, Italy.
Brini
Marisa
M
Biochemistry, University of Padova, Padova 35131, Italy; Experimental Veterinary Sciences, University of Padova, Padova 35131, Italy. Electronic address: marisa.brini@unipd.it.
D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology*; D045744:Cell Line, Tumor; D004721:Endoplasmic Reticulum / Q000235:genetics / Q000378:metabolism; D006801:Humans; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000235:genetics / Q000378:metabolism; D051605:Kv Channel-Interacting Proteins / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D009474:Neurons / Q000378:metabolism*; D024642:Potassium Channels, Voltage-Gated / Q000096:biosynthesis / Q000235:genetics; D053763:Presenilins / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000502:physiology*
D016229:Amyloid beta-Peptides; D053496:Inositol 1,4,5-Trisphosphate Receptors; C496749:KCNIP3 protein, human; D051605:Kv Channel-Interacting Proteins; D024642:Potassium Channels, Voltage-Gated; D053763:Presenilins; D012097:Repressor Proteins; D002118:Calcium