Ca2ATPases

Ca2ATPases, also known as Ca2+-ATPases, are a family of P-type ATPases that actively transport calcium ions (Ca2+) across cellular membranes by hydrolyzing ATP. They play a central role in maintaining low cytosolic Ca2+ levels and in creating high Ca2+ stores in organelles, which is essential for signaling, muscle function, secretion, and enzyme regulation.

There are several principal classes of Ca2+-ATPases. PMCA (plasma membrane Ca2+-ATPase) pumps Ca2+ out of the cell at the plasma membrane. SERCA (sarcoplasmic/endoplasmic reticulum Ca2+-ATPase) moves Ca2+ from the cytosol into the sarcoplasmic or endoplasmic reticulum. SPCA (secretory pathway Ca2+-ATPase) transports Ca2+ into the Golgi apparatus and other secretory compartments. Each class has multiple isoforms encoded by different genes, and expression patterns vary by tissue and organelle.

Mechanistically, Ca2+-ATPases belong to the P-type family that form a transient phosphoenzyme intermediate during catalysis. In the catalytic cycle, Ca2+ binds on the cytosolic side, ATP phosphorylates a conserved aspartate residue, and the ensuing conformational change releases Ca2+ on the opposite side of the membrane. Dephosphorylation resets the pump to its original state. In general, SERCA pumps two Ca2+ ions per ATP hydrolyzed, while PMCA typically transports one Ca2+ ion per ATP; SPCA pumps can also move Ca2+ efficiently, with stoichiometry that can vary among isoforms.

Regulation of these pumps varies by type. PMCA activity can be modulated by calmodulin, which relieves autoinhibition in some isoforms. SERCA activity is controlled by small regulatory peptides such as phospholamban and sarcolipin, which modulate Ca2+ affinity. Dysfunction of Ca2+-ATPases is linked to disorders in muscle, cardiac function, and secretory pathways, reflecting their essential role in Ca2+ homeostasis.