title: Physical interaction between calcineurin and Cav3.2 T-type Ca2+ channel modulates their functions.
abstract: Cav3.2 T-type Ca(2+) channel is required for the activation of calcineurin/NFAT signaling in cardiac hypertrophy. We aimed to investigate how Cav3.2 and calcineurin interact. We found that Ca(2+) and calmodulin modulate the Cav3.2/calcineurin interaction. Calcineurin binding to Cav3.2 decreases the enzyme's phosphatase activity and diminishes the channel's current density. Phenylephrine-induced hypertrophy in neonatal cardiac myocytes is reduced by a cell-permeable peptide with the calcineurin binding site sequence. These data suggest that Cav3.2 regulates calcineurin/NFAT pathway through both the Ca(2+) influx and calcineurin binding. Our findings unveiled a reciprocal regulation of Ca(2+) signaling which contributes to our understanding of cardiac hypertrophy.
authors.affiliation: Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 11490, Taiwan.
authors.forename: Ching-Hui
authors.initials: CH
authors.lastname: Huang
authors.forename: Yong-Cyuan
authors.initials: YC
authors.lastname: Chen
authors.forename: Chien-Chang
authors.initials: CC
authors.lastname: Chen
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D019703:Calcineurin / Q000378:metabolism*; D065095:Calcineurin Inhibitors; D002118:Calcium / Q000378:metabolism; D020747:Calcium Channels, T-Type / Q000737:chemistry / Q000378:metabolism*; D002147:Calmodulin / Q000378:metabolism; D004553:Electric Conductivity; D057809:HEK293 Cells; D006801:Humans; D050778:NFATC Transcription Factors / Q000378:metabolism; D011485:Protein Binding; D051381:Rats
chemical_list: C479952:CACNA1H protein, human; D065095:Calcineurin Inhibitors; D020747:Calcium Channels, T-Type; D002147:Calmodulin; D050778:NFATC Transcription Factors; D019703:Calcineurin; D002118:Calcium