Plasma membrane calcium ATPases: From generic Ca<sup>2+</sup> sump pumps to versatile systems for fine-tuning cellular Ca<sup>2+</sup>

Emanuel E. Strehler

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

The plasma membrane calcium ATPases (PMCAs) are ATP-driven primary ion pumps found in all eukaryotic cells. They are the major high-affinity calcium extrusion system for expulsion of Ca<sup>2+</sup> ions from the cytosol and help restore the low resting levels of intracellular [Ca<sup>2+</sup>] following the temporary elevation of Ca<sup>2+</sup> generated during Ca<sup>2+</sup> signaling. Due to their essential role in the maintenance of cellular Ca<sup>2+</sup> homeostasis they were initially thought to be "sump pumps" for Ca<sup>2+</sup> removal needed by all cells to avoid eventual calcium overload. The discovery of multiple PMCA isoforms and alternatively spliced variants cast doubt on this simplistic assumption, and revealed instead that PMCAs are integral components of highly regulated multi-protein complexes fulfilling specific roles in calcium-dependent signaling originating at the plasma membrane. Biochemical, genetic, and physiological studies in gene-manipulated and mutant animals demonstrate the important role played by specific PMCAs in distinct diseases including those affecting the peripheral and central nervous system, cardiovascular disease, and osteoporosis. Human PMCA gene mutations and allelic variants associated with specific disorders continue to be discovered and underline the crucial role of different PMCAs in particular cells, tissues and organs.

Original languageEnglish (US)
Pages (from-to)26-33
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume460
Issue number1
DOIs
StatePublished - May 19 2015

Fingerprint

Plasma Membrane Calcium-Transporting ATPases
Sump pumps
Tuning
Calcium
Genes
Ion Pumps
Calcium Signaling
Central Nervous System Diseases
Peripheral Nervous System
Neurology
Eukaryotic Cells
Cell membranes
Cytosol
Osteoporosis
Extrusion
Molecular Biology
Protein Isoforms
Animals
Homeostasis
Cardiovascular Diseases

Keywords

  • ATP2B ion pumps
  • Calcium microdomain
  • Calcium signaling
  • Plasma membrane calcium ATPase
  • PMCA disease

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology

Cite this

@article{12eb891de52346968e02aa42ea60fecf,
title = "Plasma membrane calcium ATPases: From generic Ca2+ sump pumps to versatile systems for fine-tuning cellular Ca2+",
abstract = "The plasma membrane calcium ATPases (PMCAs) are ATP-driven primary ion pumps found in all eukaryotic cells. They are the major high-affinity calcium extrusion system for expulsion of Ca2+ ions from the cytosol and help restore the low resting levels of intracellular [Ca2+] following the temporary elevation of Ca2+ generated during Ca2+ signaling. Due to their essential role in the maintenance of cellular Ca2+ homeostasis they were initially thought to be {"}sump pumps{"} for Ca2+ removal needed by all cells to avoid eventual calcium overload. The discovery of multiple PMCA isoforms and alternatively spliced variants cast doubt on this simplistic assumption, and revealed instead that PMCAs are integral components of highly regulated multi-protein complexes fulfilling specific roles in calcium-dependent signaling originating at the plasma membrane. Biochemical, genetic, and physiological studies in gene-manipulated and mutant animals demonstrate the important role played by specific PMCAs in distinct diseases including those affecting the peripheral and central nervous system, cardiovascular disease, and osteoporosis. Human PMCA gene mutations and allelic variants associated with specific disorders continue to be discovered and underline the crucial role of different PMCAs in particular cells, tissues and organs.",
keywords = "ATP2B ion pumps, Calcium microdomain, Calcium signaling, Plasma membrane calcium ATPase, PMCA disease",
author = "Strehler, {Emanuel E.}",
year = "2015",
month = "5",
day = "19",
doi = "10.1016/j.bbrc.2015.01.121",
language = "English (US)",
volume = "460",
pages = "26--33",
journal = "Biochemical and Biophysical Research Communications",
issn = "0006-291X",
publisher = "Academic Press Inc.",
number = "1",

}

TY - JOUR

T1 - Plasma membrane calcium ATPases

T2 - From generic Ca2+ sump pumps to versatile systems for fine-tuning cellular Ca2+

AU - Strehler, Emanuel E.

PY - 2015/5/19

Y1 - 2015/5/19

N2 - The plasma membrane calcium ATPases (PMCAs) are ATP-driven primary ion pumps found in all eukaryotic cells. They are the major high-affinity calcium extrusion system for expulsion of Ca2+ ions from the cytosol and help restore the low resting levels of intracellular [Ca2+] following the temporary elevation of Ca2+ generated during Ca2+ signaling. Due to their essential role in the maintenance of cellular Ca2+ homeostasis they were initially thought to be "sump pumps" for Ca2+ removal needed by all cells to avoid eventual calcium overload. The discovery of multiple PMCA isoforms and alternatively spliced variants cast doubt on this simplistic assumption, and revealed instead that PMCAs are integral components of highly regulated multi-protein complexes fulfilling specific roles in calcium-dependent signaling originating at the plasma membrane. Biochemical, genetic, and physiological studies in gene-manipulated and mutant animals demonstrate the important role played by specific PMCAs in distinct diseases including those affecting the peripheral and central nervous system, cardiovascular disease, and osteoporosis. Human PMCA gene mutations and allelic variants associated with specific disorders continue to be discovered and underline the crucial role of different PMCAs in particular cells, tissues and organs.

AB - The plasma membrane calcium ATPases (PMCAs) are ATP-driven primary ion pumps found in all eukaryotic cells. They are the major high-affinity calcium extrusion system for expulsion of Ca2+ ions from the cytosol and help restore the low resting levels of intracellular [Ca2+] following the temporary elevation of Ca2+ generated during Ca2+ signaling. Due to their essential role in the maintenance of cellular Ca2+ homeostasis they were initially thought to be "sump pumps" for Ca2+ removal needed by all cells to avoid eventual calcium overload. The discovery of multiple PMCA isoforms and alternatively spliced variants cast doubt on this simplistic assumption, and revealed instead that PMCAs are integral components of highly regulated multi-protein complexes fulfilling specific roles in calcium-dependent signaling originating at the plasma membrane. Biochemical, genetic, and physiological studies in gene-manipulated and mutant animals demonstrate the important role played by specific PMCAs in distinct diseases including those affecting the peripheral and central nervous system, cardiovascular disease, and osteoporosis. Human PMCA gene mutations and allelic variants associated with specific disorders continue to be discovered and underline the crucial role of different PMCAs in particular cells, tissues and organs.

KW - ATP2B ion pumps

KW - Calcium microdomain

KW - Calcium signaling

KW - Plasma membrane calcium ATPase

KW - PMCA disease

UR - http://www.scopus.com/inward/record.url?scp=84929377270&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84929377270&partnerID=8YFLogxK

U2 - 10.1016/j.bbrc.2015.01.121

DO - 10.1016/j.bbrc.2015.01.121

M3 - Article

C2 - 25998731

AN - SCOPUS:84929377270

VL - 460

SP - 26

EP - 33

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

SN - 0006-291X

IS - 1

ER -