title: PICK1 binds to calcineurin B and modulates the NFAT activity in PC12 cells.
abstract: In the central nervous system, calcineurin has been implicated in a number of Ca2+-sensitive pathways, including the regulation of neurotransmitter release and modulation of synaptic plasticity. PDZ domain-containing proteins also play an important role in the targeting and clustering of synaptic proteins. Using a yeast two-hybrid screen, we herein identified the PDZ domain-containing protein PICK1 as a specific interactor of calcineurin B. The interaction of calcineurin B and PICK1 was confirmed by GST pull-down assay in HEK293 cells and immunoprecipitation using rat brain lysate. Calcineurin B contains the consensus C-terminal peptide sequence required for interacting with the PDZ domain. The deletion of this sequence was sufficient to abolish the interaction between calcineurin B and PICK1. In addition, the knockdown of PICK1 by RNA interference inhibited the calcineurin-dependent activation of NFAT in PC12 cells. These results suggest that PICK1 may be a positive regulator of calcineurin in the central nervous system.
authors.affiliation: Department of Pharmacology, Osaka University Graduate School of Dentistry, Suita, Osaka 565-0871, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Iida
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Egusa
authors.forename: Makio
authors.initials: M
authors.lastname: Saeki
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Yatani
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Kamisaki