Cardiomyocyte calcineurin signaling in subcellular domains: From the sarcolemma to the nucleus and beyond

► Calcineurin is activated in subcellular domains by high local calcium and contact with targets. ► In a sarcolemmal microdomain calcineurin dephosphorylates NFAT which translocates to the nucleus. ► Calcineurin itself translocates to the nucleus to enhance NFAT dependent prohypertrophic effects. ► Calcineurin dephosphorylates MEF2 in vicinity to the SR or Drp1 and Bad in association with mitochondria.