SERCA3, ubiquitous but specific calcium pumps?

The calcium ion (Ca²⁺) is an important second messenger for the organism, participating in the regulation of various physiological responses in all cell types. In view of its crucial role, maintaining calcium homeostasis is important. This is why many players tightly regulate calcium homeostasis. These include a type of transporter historically located in the sarcoplasmic or endoplasmic reticulum (SR or ER), called Sarco-Endoplasmic Reticulum Ca²⁺-ATPase or SERCA calcium pumps (Toyoshima et al., 2000). Existence of these pumps was first demonstrated in the 1960s in rabbit skeletal muscle (Ebashi and Lipmann, 1962). In the mid-80s, only two families of these transporters, SERCA1 and SERCA2, were described in the skeletal muscle and the cardiovascular system, respectively. However, the existence of a third family, named SERCA3, was subsequently revealed. In this review, we present an overview of the current knowledge of the SERCA3. We firstly present the structure of this pump from its gene to the protein and its catalytic properties, highlighting its specific features compared to other isoforms. We then focus on the pathophysiological settings by describing its functional role established in several organs and pointing out the studies assuming its implication in different diseases such as obesity or cancers.