Figure 1.

Primary active transporters in the cell. (A) Schematic representation of a cell, depicting the subcellular localization of primary active Ca²⁺-transporters, which generate steep Ca²⁺ gradients across various cellular membranes (Ca²⁺ concentrations are shown in gray). Sarco(endo)plasmic reticulum Ca²⁺-ATPase (SERCA) isoforms are expressed in the ER, Golgi/secretory pathway Ca²⁺-ATPase (SPCA) isoforms are expressed throughout the Golgi apparatus and secretory vesicles, and plasma membrane Ca²⁺-ATPase (PMCA) isoforms are present in the plasma membrane. Although SERCA transports two Ca²⁺ ions per ATP, SPCA and PMCA transport only one Ca²⁺ per ATP. All Ca²⁺-ATPases present a similar domain organization (one transmembrane [TM] domain, and three cytosolic domains: A, actuator domain; P, phosphorylation domain; and N, nucleotide-binding domain). (B) Post–Albers cycle of SERCA1a is depicted, which serves as the reference Ca²⁺ transporter. The cycle shows four major conformational states of the Ca²⁺ pump (the high Ca²⁺ affinity forms E1, E1 ∼ P; and low Ca²⁺ affinity forms E2-P, E2). All Ca²⁺-ATPases belong to the P-type ATPases that transiently undergo catalytic autophosphorylation during transport. The phosphorylation and dephosphorylation reactions control, respectively, the closure of the cytosolic and luminal gates, resulting in occluded intermediates. SERCA1a is a 2Ca²⁺/2-3H⁺ countertransporter.