Molecular Diversity of Plasma Membrane Ca2+ Transporting ATPases: Their Function Under Normal and Pathological Conditions

  • Luca Hegedűs
  • Boglárka Zámbó
  • Katalin Pászty
  • Rita Padányi
  • Karolina Varga
  • John T. Penniston
  • Ágnes EnyediEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1131)


Plasma membrane Ca2+ transport ATPases (PMCA1-4, ATP2B1-4) are responsible for removing excess Ca2+ from the cell in order to keep the cytosolic Ca2+ ion concentration at the low level essential for normal cell function. While these pumps take care of cellular Ca2+ homeostasis they also change the duration and amplitude of the Ca2+ signal and can create Ca2+ gradients across the cell. This is accomplished by generating more than twenty PMCA variants each having the character – fast or slow response, long or short memory, distinct interaction partners and localization signals – that meets the specific needs of the particular cell-type in which they are expressed. It has become apparent that these pumps are essential to normal tissue development and their malfunctioning can be linked to different pathological conditions such as certain types of neurodegenerative and heart diseases, hearing loss and cancer. In this chapter we summarize the complexity of PMCA regulation and function under normal and pathological conditions with particular attention to recent developments of the field.


Plasma membrane Ca2+ ATPase (PMCA) ATP2B1-4 Alternative splice Calmodulin Phosphatidylinositol-45-bisphosphate Actin cytoskeleton Ca2+ signal Genetic variation Altered expression Pathological condition 



Alzheimer’s disease


adenosine triphosphate




calcium/calmodulin-dependent protein kinase II


calcium/calmodulin-dependent serine protein kinase


calmodulin binding sequence


endoplasmic reticulum


extracellular-signal regulated kinase


histone deacetylase


human epidermal growth factor receptor 2


human umbilical vein endothelial cell


inositol 1,4,5-trisphosphate


inositol 1,4,5-trisphosphate receptor


immunological synapse


membrane-associated guanylate kinase


mouse lung endothelial cells


nuclear factor of activated T-cell


Na+/H+ exchanger regulatory factor 2


neural nitric oxide synthase


phosphatidylinositol-4,5- bisphosphate


protein kinase C


protein kinase A


plasma membrane Ca2+ ATPases


partner of STIM


post synaptic density protein 95


nuclear factor κB ligand


Ras association domain-containing protein 1


red blood cell


sickle cell disease


sarco/endoplasmic reticulum Ca2+ ATPases


small nucleotide polymorphisms


store operated Ca2+ entry


secretory-pathway Ca2+ ATPase


stromal interacting molecule


transforming growth factor

TM domain

transmembrane domain


trichostatin A


vascular endothelial growth factor


vascular smooth muscle cell



The authors are supported by grants from the Hungarian Scientific Research Funds NKFIH K119223 and FIKP-EMMI (AE).


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Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  • Luca Hegedűs
    • 1
  • Boglárka Zámbó
    • 2
  • Katalin Pászty
    • 3
  • Rita Padányi
    • 4
  • Karolina Varga
    • 4
  • John T. Penniston
    • 5
  • Ágnes Enyedi
    • 4
    Email author
  1. 1.Department of Thoracic Surgery, RuhrlandklinikUniversity Clinic EssenEssenGermany
  2. 2.Research Centre for Natural SciencesInstitute of Enzymology, Hungarian Academy of SciencesBudapestHungary
  3. 3.Department of BiophysicsSemmelweis UniversityBudapestHungary
  4. 4.2nd Department of PathologySemmelweis UniversityBudapestHungary
  5. 5.Department of NeurosurgeryMassachusetts General HospitalBostonUSA

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