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PMID: 10318964 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Calcineurin controls inositol 1,4,5-trisphosphate type 1 receptor expression in neurons.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 96 ·No. 10 ·1999-05-11 ·Pages 5797-801

Genazzani AA, Carafoli E, Guerini D

Abstract

In the central nervous system, release of Ca2+ from intracellular stores contributes to numerous functions, including neurotransmitter release and long-term potentiation and depression. We have investigated the developmental profile and the regulation of inositol 1,4,5-trisphosphate receptor (IP3R) and ryanodine receptor (RyR) in primary cultures of cerebellar granule cells. The expression of both receptor types increases during development. Whereas the expression of type 1 IP3R appears to be regulated by Ca2+ influx through L type channels or N-methyl-D-aspartate (NMDA) receptors, RyR levels increase independently of Ca2+. The main target of Ca2+-influx-regulating IP3R expression is the Ca2+ calmodulin-dependent protein phosphatase calcineurin, because pharmacological blockade of this protein abolishes IP3R expression. Although calcineurin has been shown to regulate the phosphorylation state of the IP3R, the effect described here is at the transcriptional level because IP3R mRNA changes in parallel with protein levels. Thus, calcineurin plays a dual role in IP3R-mediated Ca2+ signaling: it regulates IP3R function by dephosphorylation in the short-term time scale and IP3R expression over more extended periods.

MeSH Terms
Animals Calcineurin/genetics,metabolism Calcium Channels/metabolism Calcium-Transporting ATPases/metabolism Cation Transport Proteins Cells, Cultured Central Nervous System/metabolism Cerebellum/metabolism Cyclosporine/pharmacology Gene Expression Regulation/genetics Inositol 1,4,5-Trisphosphate Receptors Phosphorylation Plasma Membrane Calcium-Transporting ATPases RNA, Messenger/metabolism Rats Rats, Wistar Receptors, Cytoplasmic and Nuclear/metabolism Reverse Transcriptase Polymerase Chain Reaction Ryanodine Receptor Calcium Release Channel/metabolism Tacrolimus/pharmacology Transcription, Genetic Up-Regulation
Chemicals
Calcium Channels Cation Transport Proteins Inositol 1,4,5-Trisphosphate Receptors RNA, Messenger Receptors, Cytoplasmic and Nuclear Ryanodine Receptor Calcium Release Channel Cyclosporine Calcineurin Plasma Membrane Calcium-Transporting ATPases Calcium-Transporting ATPases Tacrolimus
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Genazzani A A
Department of Biochemistry III, Swiss Federal Institute of Technology, 8092 Zurich, Switzerland.
Carafoli E
Guerini D
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.96.10.5797
Published
1999-05-11
Pages
5797-801
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC21940
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.96.10.5797 PMC Full Text View journal details
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