Beyond Intracellular Signaling: The Ins and Outs of Second Messengers Microdomains

  • Riccardo Filadi
  • Emy Basso
  • Konstantinos Lefkimmiatis
  • Tullio PozzanEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 981)


A typical characteristic of eukaryotic cells compared to prokaryotes is represented by the spatial heterogeneity of the different structural and functional components: for example, most of the genetic material is surrounded by a highly specific membrane structure (the nuclear membrane), continuous with, yet largely different from, the endoplasmic reticulum (ER); oxidative phosphorylation is carried out by organelles enclosed by a double membrane, the mitochondria; in addition, distinct domains, enriched in specific proteins, are present in the plasma membrane (PM) of most cells. Less obvious, but now generally accepted, is the notion that even the concentration of small molecules such as second messengers (Ca2+ and cAMP in particular) can be highly heterogeneous within cells. In the case of most organelles, the differences in the luminal levels of second messengers depend either on the existence on their membrane of proteins that allow the accumulation/release of the second messenger (e.g., in the case of Ca2+, pumps, exchangers or channels), or on the synthesis and degradation of the specific molecule within the lumen (the autonomous intramitochondrial cAMP system). It needs stressing that the existence of a surrounding membrane does not necessarily imply the existence of a gradient between the cytosol and the organelle lumen. For example, the nuclear membrane is highly permeable to both Ca2+ and cAMP (nuclear pores are permeable to solutes up to 50 kDa) and differences in [Ca2+] or [cAMP] between cytoplasm and nucleoplasm are not seen in steady state and only very transiently during cell activation. A similar situation has been observed, as far as Ca2+ is concerned, in peroxisomes.


Ca2+ signaling cAMP ATP Second messengers Microdomains cAMP sensors Ca2+ sensors ER Mitochondria PKA PDE 



The original work by the Authors has been supported by grants from the Italian Ministry of University and Research (MIUR), by Telethon Foundation, by Cariparo Foundation, by the National Research Council (CNR) and by the University of Padova to TP. We are grateful to Dr. P. Magalhaes for critically reading the manuscript.


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© Springer International Publishing AG, part of Springer Nature 2017

Authors and Affiliations

  • Riccardo Filadi
    • 1
  • Emy Basso
    • 2
  • Konstantinos Lefkimmiatis
    • 2
    • 3
  • Tullio Pozzan
    • 1
    • 2
    • 3
    Email author
  1. 1.Department of Biomedical SciencesUniversity of PadovaPadovaItaly
  2. 2.Institute of Neuroscience, Padova SectionNational Research CouncilPadovaItaly
  3. 3.Venetian Institute of Molecular MedicinePadovaItaly

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