The Ca2+-ATPase pump facilitates bidirectional proton transport across the sarco/endoplasmic reticulum

L. Michel Espinoza-Fonseca

Research output: Contribution to journalReview articlepeer-review

7 Scopus citations

Abstract

Ca2+ transport across the sarco/endoplasmic reticulum (SR) plays an essential role in intracellular Ca2+ homeostasis, signalling, cell differentiation and muscle contractility. During SR Ca2+ uptake and release, proton fluxes are required to balance the charge deficit generated by the exchange of Ca2+ and other ions across the SR. During Ca2+ uptake by the SR Ca2+-ATPase (SERCA), two protons are countertransported from the SR lumen to the cytosol, thus partially compensating for the charge moved by Ca2+ transport. Studies have shown that protons are also transported from the cytosol to the lumen during Ca2+ release, but a transporter that facilitates proton transport into the SR lumen has not been described. In this article we propose that SERCA forms pores that facilitate bidirectional proton transport across the SR. We describe the location and structure of water-filled pores in SERCA that form cytosolic and luminal pathways for protons to cross the SR membrane. Based on this structural information, we suggest mechanistic models for proton translocation to the cytosol during active Ca2+ transport, and into the SR lumen during SERCA inhibition by endogenous regulatory proteins. Finally, we discuss the physiological consequences of SERCA-mediated bidirectional proton transport across the SR membrane of muscle and non-muscle cells.

Original languageEnglish (US)
Pages (from-to)633-637
Number of pages5
JournalMolecular BioSystems
Volume13
Issue number4
DOIs
StatePublished - 2017

Bibliographical note

Funding Information:
The author was supported by the National Institutes of Health grant R01GM120142.

Fingerprint Dive into the research topics of 'The Ca<sup>2+</sup>-ATPase pump facilitates bidirectional proton transport across the sarco/endoplasmic reticulum'. Together they form a unique fingerprint.

Cite this