Primary Active Ca²⁺ Transport Systems in Health and Disease

Abstract

Calcium ions (Ca 2+ ) are prominent cell signaling effectors that regulate a wide variety of cellular processes. Among the different players in Ca 2+ homeostasis, primary active Ca 2+ transporters are responsible for keeping low basal Ca 2+ levels in the cytosol while establishing steep Ca 2+ gradients across intracellular membranes or the plasma membrane. This review summarizes our current knowledge on the three types of primary active Ca 2+ -ATPases: the sarco(endo)plasmic reticulum Ca 2+ -ATPase (SERCA) pumps, the secretory pathway Ca 2+ -ATPase (SPCA) isoforms, and the plasma membrane Ca 2+ -ATPase (PMCA) Ca 2+ -transporters. We first discuss the Ca 2+ transport mechanism of SERCA1a, which serves as a reference to describe the Ca 2+ transport of other Ca 2+ pumps. We further highlight the common and unique features of each isoform and review their structure-function relationship, expression pattern, regulatory mechanisms, and specific physiological roles. Finally, we discuss the increasing genetic and in vivo evidence that links the dysfunction of specific Ca 2+ -ATPase isoforms to a broad range of human pathologies, and highlight emerging therapeutic strategies that target Ca 2+ pumps.

Protein Adsorption on Solid Supported Membranes: Monitoring the Transport Activity of P-Type ATPases

“…The SERCA enzyme is one of the most investigated P-type ATPase [ 15 , 16 , 37 , 38 , 39 ]. In muscle cells, SERCA couples the energy gained by the hydrolysis of one ATP molecule to the transport of two Ca 2+ ions against their electrochemical potential gradient from the cytoplasm into the lumen of SR, which is the main intracellular Ca 2+ storage organelle.…”

“…Ca 2+ uptake in the SR lumen by SERCA plays an essential role in regulating cytoplasmic Ca 2+ concentration, which is kept at or below 0.1 µM; in this manner, SERCA induces muscle relaxation and contributes to intracellular Ca 2+ homeostasis. Modified SERCA expression and impaired pumping activity have been associated with pathological conditions and several diseases with a wide range of severity [ 39 , 40 ].…”

Protein Docking and Steered Molecular Dynamics Reveal Alternative Regulatory Sites on the SERCA Calcium Transporter

“…The sarco(endo)plasmic reticulum Ca 2+ -ATPase (SERCA) is responsible for sequestering calcium into the sarcoplasmic and endoplasmic reticulum, creating a reservoir for intracellular Ca 2+ signaling. This transporter is important in all cell types, and it is tightly controlled in cells where Ca 2+ handling must rapidly adjust to changing physiological demands (1,2). A prime example is the regulation of SERCA transport activity in cardiac muscle cells.…”

Time Domain Dielectric Spectroscopic Studies of Potassium Oleate and Cetyl Pyridinium Chloride in Acetate Buffer Solution

“…[1][2][3][4] In addition, several fundamental scientific interests lie behind surfactant systems in the fields of physical chemistry and biology. [5,6] Surfactant molecules which are made up of polar, ionic, nonionic head groups in aqueous solution self-assemble into micelles at concentrations above the so-called critical micelle concentration (cmc).The self-aggregating property of many surfactants that leads to micelle formation makes the system more complex but effective toward various applications.…”