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The SarcoEndoplasmic Reticulum Calcium ATPase

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Book cover Membrane Protein Complexes: Structure and Function

Part of the book series: Subcellular Biochemistry ((SCBI,volume 87))

Abstract

The calcium pump (a.k.a. Ca2+-ATPase or SERCA) is a membrane transport protein ubiquitously found in the endoplasmic reticulum (ER) of all eukaryotic cells. As a calcium transporter, SERCA maintains the low cytosolic calcium level that enables a vast array of signaling pathways and physiological processes (e.g. synaptic transmission, muscle contraction, fertilization). In muscle cells, SERCA promotes relaxation by pumping calcium ions from the cytosol into the lumen of the sarcoplasmic reticulum (SR), the main storage compartment for intracellular calcium. X-ray crystallographic studies have provided an extensive understanding of the intermediate states that SERCA populates as it progresses through the calcium transport cycle. Historically, SERCA is also known to be regulated by small transmembrane peptides, phospholamban (PLN) and sarcolipin (SLN). PLN is expressed in cardiac muscle, whereas SLN predominates in skeletal and atrial muscle. These two regulatory subunits play critical roles in cardiac contractility. While our understanding of these regulatory mechanisms are still developing, SERCA and PLN are one of the best understood examples of peptide-transporter regulatory interactions. Nonetheless, SERCA appeared to have only two regulatory subunits, while the related sodium pump (a.k.a. Na+, K+-ATPase) has at least nine small transmembrane peptides that provide tissue specific regulation. The last few years have seen a renaissance in our understanding of SERCA regulatory subunits. First, structures of the SERCA-SLN and SERCA-PLN complexes revealed molecular details of their interactions. Second, an array of micropeptides concealed within long non-coding RNAs have been identified as new SERCA regulators. This chapter will describe our current understanding of SERCA structure, function, and regulation.

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Abbreviations

Å:

Angstrom

ADP:

Adenosine Diphosphate

AKAP:

A Kinase Anchoring Protein

Akt:

Protein Kinase B

AlF4 :

Aluminum Tetrafluoride

ALN:

Another-Regulin

AMP:

Adenosine Monophosphate

AMPPCP:

Phosphomethylphosphonic Acid Adenylate Ester

ATP:

Adenosine triphosphate

CAMKII:

Calcium/Calmodulin Dependent Protein Kinase II

CPA:

Cyclopiazonic acid

dSCLa:

Drosophila Sarcolamban Isoform A

dSCLb:

Drosophila Sarcolamban Isoform B

DWORF:

Dwarf Open Reading Frame

ELN:

Endoregulin

ER:

Endoplasmic Reticulum

GDP:

Guanosine Diphosphate

GTP:

Guanosine Triphosphate

HAX1:

HS-1 Associated Protein

hDWORF:

Human Dwarf Open Reading Frame

hMLN:

Human Myoregulin

hPLN:

Human Phospholamban

Hsp20:

Small Heat Shock Protein 20

hSLN:

Human Sarcolipin

I-1:

Inhibitor-1

KCa :

Apparent Calcium Affinity

mALN:

Mouse Another-Regulin

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Primeau, J.O., Armanious, G.P., Fisher, M.E., Young, H.S. (2018). The SarcoEndoplasmic Reticulum Calcium ATPase. In: Harris, J., Boekema, E. (eds) Membrane Protein Complexes: Structure and Function. Subcellular Biochemistry, vol 87. Springer, Singapore. https://doi.org/10.1007/978-981-10-7757-9_8

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