PICK1 binds to calcineurin B and modulates the NFAT activity in PC12 cells |
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Authors: | Iida Tsutomu Egusa Hiroshi Saeki Makio Yatani Hirofumi Kamisaki Yoshinori |
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Affiliation: | a Department of Pharmacology, Osaka University Graduate School of Dentistry, Suita, Osaka 565-0871, Japan b Department of Fixed Prosthodontics, Osaka University Graduate School of Dentistry, Division of Oromaxillofacial Regeneration, 1-8 Yamadaoka, Suita, Osaka 565-0871, Japan c E-Institute of Shanghai Universities, Division of Nitric Oxide and Inflammatory Medicine, Shanghai, China |
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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. |
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Keywords: | Calcineurin B PICK1 NFAT PDZ domain Yeast two-hybrid screening |
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