Widespread control of calcium signaling by a family of SERCA-inhibiting micropeptides

Douglas M. Anderson, Catherine A. Makarewich, Kelly M. Anderson, John M. Shelton, Svetlana Bezprozvannaya, Rhonda Bassel-Duby, Eric N. Olson

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Micropeptides function as master regulators of calcium-dependent signaling in muscle. Sarco/endoplasmic reticulum Ca2+ ATPase (SERCA), the membrane pump that promotes muscle relaxation by taking up Ca2+ into the sarcoplasmic reticulum, is directly inhibited by three muscle-specific micropeptides: myoregulin (MLN), phospholamban (PLN), and sarcolipin (SLN). The widespread and essential function of SERCA across diverse cell types has raised questions as to how SERCA is regulated in cells that lack MLN, PLN, and SLN. We identified two transmembrane micropeptides, endoregulin (ELN) and another-regulin (ALN), that share key amino acids with their muscle-specific counterparts and function as direct inhibitors of SERCA pump activity. The distribution of transcripts encoding ELN and ALN mirrored that of SERCA isoform-encoding transcripts in nonmuscle cell types. Our findings identify additional members of the SERCA-inhibitory micropeptide family, revealing a conserved mechanism for the control of intracellular Ca2+ dynamics in both muscle and nonmuscle cell types.

Original languageEnglish (US)
Article numberra119
JournalScience Signaling
Volume9
Issue number457
DOIs
StatePublished - Dec 6 2016

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Sarcoplasmic Reticulum Calcium-Transporting ATPases
Calcium Signaling
Muscle
Calcium
Muscles
Pumps
Muscle Relaxation
Sarcoplasmic Reticulum
Calmodulin
Muscle Cells
Protein Isoforms
Membranes
Amino Acids

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Widespread control of calcium signaling by a family of SERCA-inhibiting micropeptides. / Anderson, Douglas M.; Makarewich, Catherine A.; Anderson, Kelly M.; Shelton, John M.; Bezprozvannaya, Svetlana; Bassel-Duby, Rhonda; Olson, Eric N.

In: Science Signaling, Vol. 9, No. 457, ra119, 06.12.2016.

Research output: Contribution to journalArticle

Anderson DM, Makarewich CA, Anderson KM, Shelton JM, Bezprozvannaya S, Bassel-Duby R et al. Widespread control of calcium signaling by a family of SERCA-inhibiting micropeptides. Science Signaling. 2016 Dec 6;9(457). ra119. https://doi.org/10.1126/scisignal.aaj1460
Anderson, Douglas M. ; Makarewich, Catherine A. ; Anderson, Kelly M. ; Shelton, John M. ; Bezprozvannaya, Svetlana ; Bassel-Duby, Rhonda ; Olson, Eric N. / Widespread control of calcium signaling by a family of SERCA-inhibiting micropeptides. In: Science Signaling. 2016 ; Vol. 9, No. 457.
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