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

• DOI: 10.1073/pnas.96.10.5797
• Publication Date: 2002-07-26T14:39:15Z
• Authors: Armando A. Genazzani; Ernesto Carafoli; Danilo Guerini
• Keywords: Inositol trisphosphate receptor; Inositol trisphosphate; Dephosphorylation; Calcium Signaling

In the central nervous system, release of Ca 2+ from intracellular stores contributes to numerous functions, including neurotransmitter and long-term potentiation depression. We have investigated developmental profile regulation inositol 1,4,5-trisphosphate receptor (IP3R) ryanodine (RyR) in primary cultures cerebellar granule cells. The expression both types increases during development. Whereas type 1 IP3R appears be regulated by influx through L channels or N -methyl- d -aspartate (NMDA) receptors, RyR levels increase independently . main target -influx-regulating is calmodulin-dependent protein phosphatase calcineurin, because pharmacological blockade this abolishes expression. Although calcineurin has been shown regulate phosphorylation state IP3R, effect described here at transcriptional level mRNA changes parallel with levels. Thus, plays a dual role IP3R-mediated signaling: it regulates function dephosphorylation short-term time scale over more extended periods.