Role of SERCA2b in mobilization of nuclear Ca2+ in HeLa cells.

Abstract

Ca2+ liberation from the endoplasmic reticulum activates sarco-endoplasmic reticulum ATPase (SERCA) to return Ca2+ to storage. We explored the role of SERCA in dynamic changes of intranuclear Ca2+ in single HeLa cells. Application of forskolin, as an activator of SERCA, caused the phosphorylation of SERCA2b but not SERCA3 on serine residues, which increased the rate of Ca2+ uptake. Forskolin also induced the changes of Ca2+ movement pattern in the nucleus when cells were stimulated with the Ca2+-releasing agents, histamine or A23187. Immunofluorescence staining showed that SERCA2b was densely populated on special parts of the nuclear envelope, but SERCA3 only existed in endoplasmic reticulum. Injection of an anti-SERCA2 antibody into the cytoplasm blocked the rise in the nuclear Ca2+ concentration ([Ca2+]n). However, injection of an anti-SERCA3 antibody did not affect the initiation of Ca2+ oscillations in the nucleus. Our data suggest that the activated-SERCA2b elevates the rate of uptake of free Ca2+ into stores along the nuclear envelope, which might support and maintain the nuclear Ca2+ homeostasis.