Presenilin 1 regulates endoplasmic reticulum calcium transport by cardiac SERCA and RyR

Presenilin 1 (PS1) is a transmembrane protein localized in the endoplasmic reticulum (ER) of different cell types. PS1 acts as catalytic subunit of the γ-secretase complex. Impaired γ- secretase activity due to PS1 mutants in neurons is recognized one of the leading causes of Alzheimer’s disease (AD). Furthermore, PS1 mutants associated with AD cause Ca2+ homeostasis imbalances. PS1 is also expressed in the heart, but its role in regulation of cardiac Ca2+ homeostasis remains largely unknown. Here, we studied the role of PS1 in regulation of ER Ca2+ transport in HEK293 cells transiently expressing human cardiac ER Ca2+ ATPase (SERCA2a) and human cardiac ryanodine receptor (RyR2).