SERCA

SERCA, or sarco/endoplasmic reticulum Ca²⁺-ATPase, or SR Ca²⁺-ATPase, is a calcium ATPase-type P-ATPase.

Function

SERCA resides in the sarcoplasmic reticulum (SR) within muscle cells. It is a Ca²⁺ ATPase that transfers Ca²⁺ from the cytosol of the cell to the lumen of the SR at the expense of ATP hydrolysis during muscle relaxation.

There are 3 major domains on the cytoplasmic face of SERCA: the phosphorylation and nucleotide-binding domains, which form the catalytic site, and the actuator domain, which is involved in the transmission of major conformational changes.

It seems that, in addition to the calcium-transporting properties, SERCA1 generates heat in some adipocytes and can improve cold tolerance in some wood frog.

Regulation

The rate at which SERCA moves Ca²⁺ across the SR membrane can be controlled by the regulatory protein phospholamban (PLB/PLN). SERCA is normally inhibited by PLB, with which it is closely associated. Increased β-adrenergic stimulation reduces the association between SERCA and PLB by the phosphorylation of PLB by PKA. When PLB is associated with SERCA, the rate of Ca²⁺ movement is reduced; upon dissociation of PLB, Ca²⁺ movement increases.

Another protein, calsequestrin, binds calcium within the SR and helps to reduce the concentration of free calcium within the SR, which assists SERCA so that it does not have to pump against such a high concentration gradient. The SR has a much higher concentration of Ca²⁺ (10,000x) inside when compared to the cytoplasmic Ca²⁺ concentration. SERCA2 can be regulated by microRNAs, for instance miR-25 suppresses SERCA2 in heart failure.

For experimental reasons, SERCA can be inhibited by thapsigargin and induced by istaroxime.

Paralogs

There are 3 major paralogs, SERCA1-3, which are expressed at various levels in different cell types.

• ATP2A1 - SERCA1
• ATP2A2 - SERCA2
• ATP2A3 - SERCA3

There are additional post-translational isoforms of both SERCA2 and SERCA3, which serve to introduce the possibility of cell-type-specific Ca²⁺-reuptake responses as well as increasing the overall complexity of the Ca²⁺ signaling mechanism.

External links

• Sarcoplasmic Reticulum Calcium-Transporting ATPases at the US National Library of Medicine Medical Subject Headings (MeSH)

http://en.m.wikipedia.org/wiki/Mir-25_microRNA_precursor_family