Ca2+ and cAMP signalling in physiology and pathology

Foto gruppo Ca2+ and cAMP signalling in physiology and pathology

cell signallingHistorically, our lab has been interested in calcium (Ca2+) homeostasis and its role in cell signalling, in both health and disease. In the last years, different projects centred on cellular Ca2+ handling in Alzheimer’s Disease (AD) were started. By analysing different familial AD cell and mouse models, expressing presenilin 2 (PS2) mutants, we have characterized alterations in intracellular Ca2+ handling, mitochondria function and brain network excitability, all features potentially linked to disease pathogenesis.

Another major topic of the lab over the last years has been the development and use of organelle targeted GFP-based fluorescent indicators for monitoring Ca2+ dynamics in living cells. These new tools, targeted to different organelles, such as Endoplasmic Reticulum (ER), Golgi apparatus, mitochondria, peroxisomes, have allowed, for the first time, to address the study of Ca2+ homeostasis in subcellular compartments for which only indirect information was available.

In addition to Ca2+, the interest of our group is also concentrated on cAMP signalling. In this context, novel tools − again targeted to subcellular regions (plasma membrane, mitochondria, nucleus) − have been generated and characterized and several signalling pathways linked to this second messenger have been detailed.

All these methodologies are used to address with novel approaches the role of second messenger heterogeneity in different physio-pathological conditions (e.g., the control of cardiac cell excitability or the pathogenesis of AD) not only in cell lines or primary cell cultures, but also in tissue preparations (acute slices) and in vivo.

  People

Faculty

  • Paola PIZZO - Associate Professor
  • Tullio POZZAN - Professor Emeritus
  • Emy BASSO - C.N.R. Researcher
  • Giulietta DI BENEDETTO - C.N.R. Researcher
  • Riccardo FILADI - C.N.R. Researcher
  • Elisa GREOTTI - C.N.R. Researcher
  • Diana PENDIN - C.N.R. Researcher
  • Cristina FASOLATO - Retired

Lab Members

  • Paloma GARCIA CASAS - Post-doctoral fellow
  • Nelly REDOLFI - Post-doctoral fellow
  • Sonia SONDA - Research fellow
  • Michela ROSSINI - PhD Student
  • Paulo Jorge MENDES PEREIRA MAGALHAES - Research assistant

  Five recent publications

  1. Filadi R, Leal NS, Schreiner B, Rossi A, Dentoni G, Pinho CM, Wiehager B, Cieri D, Calì T, Pizzo P, Ankarcrona M. TOM70 Sustains Cell Bioenergetics by Promoting IP3R3-Mediated ER to Mitochondria Ca2+ Transfer. Curr Biol. 2018 Feb 5;28(3):369-382
  2. Pendin D, Greotti E, Lefkimmiatis K, Pozzan T. Exploring cells with targeted biosensors. J Gen Physiol. 2017 Jan;149(1):1-36.
  3. Fontana R, Agostini M, Murana E, Mahmud M, Scremin E, Rubega M, Sparacino G, Vassanelli S, Fasolato C. Early hippocampal hyper-excitability in PS2APP mice: role of mutant PS2 and APP. Neurobiology of Aging 2017 Feb;50:64-76.
  4. Filadi R, Greotti E, Turacchio G, Luini A, Pozzan T, Pizzo P. Presenilin 2 Modulates Endoplasmic Reticulum-Mitochondria Coupling by Tuning the Antagonistic Effect of Mitofusin 2. Cell Rep. 2016 Jun 7;15(10):2226-2238.
  5. Di Benedetto G, Pendin D, Greotti E, Pizzo P, Pozzan T. Ca2+ and cAMP cross-talk in mitochondria. J Physiol. 2014 Jan 15;592(2):305-12