Regulation of the regulator: Endopeptidase cleavage controls the expression of a micropeptide that regulates SERCA

Taylor A Phillips; Seth L Robia

doi:10.1016/j.ceca.2022.102655

Regulation of the regulator: Endopeptidase cleavage controls the expression of a micropeptide that regulates SERCA

Cell Calcium. 2022 Nov:107:102655. doi: 10.1016/j.ceca.2022.102655. Epub 2022 Sep 22.

Authors

Taylor A Phillips¹, Seth L Robia²

Affiliations

¹ Department of Cell and Molecular Physiology, Loyola University Chicago, Maywood 60153, IL, United States of America.
² Department of Cell and Molecular Physiology, Loyola University Chicago, Maywood 60153, IL, United States of America. Electronic address: srobia@luc.edu.

PMID: 36179466
DOI: 10.1016/j.ceca.2022.102655

Abstract

Micropeptides regulate cellular calcium handling by modulating the function of the calcium transporter SERCA. In a recent Nature Communications paper [4] authors Schiemann et al. describe regulation of an invertebrate SERCA-active micropeptide, sarcolamban, by an endopeptidase called neprilysin 4 (NEP4). NEP4 activity limits sarcolamban expression by cleavage of luminal residues near the micropeptide's c-terminus. This cleavage event liberates sarcolamban from the membrane, reduces its oligomerization, and prevents it from inhibiting SERCA. The study reveals a novel mechanism for "regulation of the regulator" that may be a general feature of micropeptide/SERCA physiology.

Keywords: Endopeptidase; Membrane transport; Micropeptides; SERCA; Sarcolamban.

MeSH terms

Calcium* / metabolism
Calcium-Binding Proteins / metabolism
Endopeptidases / metabolism
Muscle Proteins / chemistry
Muscle Proteins / metabolism
Neprilysin / metabolism
Sarcoplasmic Reticulum Calcium-Transporting ATPases* / metabolism

Substances

Sarcoplasmic Reticulum Calcium-Transporting ATPases
Calcium
Muscle Proteins
Calcium-Binding Proteins
Neprilysin
Endopeptidases