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A. M. Aragay: Signaling through G proteins

Lab Presentation

The aim of this subline is to understand the process of signal transduction that let to changes in cell structure and function in physiology and diseases. We focus our attention on G proteins that are molecular switches that signal through their receptors, GPCRs, at the plasma membrane. However, a novel localization of G proteins at the mitochondria and other endomembranes where they regulate the physiology of these organelles has been recently demonstrated by our group. We focus our attention in understanding how the G proteins control the proper balance between mitochondria fusion and fission, their dynamic movement and the mitochondrial physiology. Mitochondria are dynamic organelles that produce most of the energy of the cell. Broken mitochondria cristae, and loss of internal structure impairs many of the functions of mitochondria and its present in neurons of several neurodegenerative diseases.

In order to unveil the putative effectors of G proteins that mediate those effects at the mitochondria, our group has undertaken a mass-spectrometry analysis based on G protein-immunoprecipitates from cellular endomembranes using different cell lines: “mito-intereactome”. In addition, our projects relay heavily on the use of “state of the art” imaging technologies that helps us to answer crucial questions on mitochondria dynamics and neuronal physiology.

Research Lines

The general objectives of the research subline are:

To study the dynamics of the mitochondria in hypocampal neurons
We aim to define how G proteins control the anterograde and retrograde transport of mitochondria along the axons. For this we will define the molecular partners and the mechanims of action of G proteins at the outer mitochondrial membrane and the link to the motor proteins kinesin and dynein.
To investigate if G proteins regulate mitophagy
We aim to descipher who G proteins influence the autophagosome biogenesis, its dynein-dynactin transport along microtubules or its fusion with the lysosome or contact with ER. We explore mechanisms of inhibition of G proteins that can led to mitochondrial autophagy and neuronal survival with the goal to halt the pathogenesis of Alzheimer.
Anna Aragay Combas
  • Anna M. Aragay Combas
  • IBMB-CSIC
  • C/ Baldiri i Reixac, 15
  • 08028 Barcelona, Spain
  • Phone: +34 93 4020196
  • E-mail: aarbmc@ibmb.csic.es

Principal Investigator



Past students

  • Mireia Andreu

    PhD Student

  • Georgina Garrido

    PhD Student

  • Míriam Masià

    PhD Student

  • Cristiane Beninca

    PhD Student

 

  • Selheim F, Aasebø E, Ribas C, Aragay AM. An overview on G protein-coupled receptor-induced signal transduction in Acute Myeloid Leukemia. Curr Med Chem 2019 Apr 29 doi: 10.2174/0929867326666190429153247. 
  • Pons M, Izquierdo I, Andreu-Carbó M, Garrido G, Planagumà J, Muriel O, Geli MI, Aragay AM. Regulation of chemokine receptor CCR2 recycling by filamin a phsophorylation. J Cell Sci. 2016 Dec 1. pii: jcs.193821. [Epub ahead of print]

  • Masià-Balagué M, Izquierdo I, Garrido G, Cordomí A, Pérez-Benito L, Miller NL, Schlaepfer DD, Gigoux V, Aragay AM. Gastrin-stimulated Gα13 Activation of Rgnef Protein (ArhGEF28) in DLD-1 Colon Carcinoma Cells. J Biol Chem. 2015 Jun 12;290(24):15197-209.

  • Benincá C, Planagumà J, de Freitas Shuck A, Acín-Perez R, Muñoz JP, de Almeida MM, Brown JH, Murphy AN, Zorzano A, Enríquez JA, Aragay AM. A new non-canonical pathway of Ga(q) protein regulating mitochondrial dynamics and bioenergetics. Cell Signal. 2014 26:1135-46.

  • Sánchez-Fernández G, Cabezudo S, García-Hoz C, Benincá C, Aragay AM, Mayor F Jr, Ribas Filamin C. Gaq signalling: the new and the old. Cell Signal. 2014 26:833-48.

  • Nygaard G, Herfindal L, Kopperud R, Aragay AM, Holmsen H, Døskeland SO, Kleppe R, Selheim F. Time-dependent inhibitory effects of cGMP-analogues in thrombin-induced platelet-derived microparticles formation, platelet aggregation, and P-selectin expression.Biochem Biophys Res Commun. 2014 Jul 4;449(3):357-63.

  • Planagumà J, Minsaas L, Pons M, Myhren L, Garrido G, Aragay AM. A-hinge region1-EGFP: a novel tool for tracking the cellular functions of Filamin A in real-time. PLoS One. 2012;7(8):e40864
  • Minsaas L, Planagumà J, Madziva M, Krakstad BF, Masià-Balagué M, Katz AA, Aragay AM. (2010) Filamin a binds to CCR2B and regulates its internalization.  PLoS One 5(8):e12212
     
  • Jiménez-Sainz, MC., Murga, C., KavelaarsA. , JuradoM., Fast-KraastakB., HeijnenC.J. Mayor,  F. and AragayA. M. GRK2 negatively regulates chemokine activation of ERK cascade at a level downstream from G protein subunits. (2006) Mol. Biol. Cell  Jan;17(1):25-31.
     
  • B.B. Johannson, Minsaas L.  & Aragay, A.M. Proteosome involvement in Galpha q and Galpha16 protein degradation. (2005) The FEBS J. (2005). 272, 5365-5377.
     
  • Krastad, B., V. Ardavatia & Aragay, AM. (2004) A role for Ga12/Ga13 in p120ctn regulation. Proc. Natl. Acad. Sci., 101, 10314-10319.
     
  • M.C. Jimenez, Fast, B, Mayor, F., jr. &  A.M.Aragay (2003). Mechanisms of the CCR2 chemokine receptor activation of the MAPK cascade. Mol. Pharmacol. 64, 773-782.

Estudio del mitointeratoma de Gq en las neuronas

  • Financiado por: MINECO  BFU2017-83379-R
  • Duración: 2018-2020
  • Investigador Principal: A.M. Aragay

Gq: de la mitocondria a los cardiomiocitos

  • Financiado por: MINECO  BFU2014-53978-R
  • Duración: 2015-2017
  • Investigador Principal: A.M. Aragay

Procesos de señalización por proteínas G implicados en migración celular

  • Financiado por: MINECO BFU2011-30080 
  • Duración: 2012-2014
  • Investigador Principal: A.M. Aragay

Estudio de la interacción de la proteína G12 con p120 catenina

  • Financiado por:MINISTERIO DE CIENCIA E INNOVACION BFU2008-04262                  
  • Duración: 2009-2011
  • Investigador Principal: A. M. Aragay

Mecanisme i funció del tràfic endocític

  • Financiado por:  AGAUR  SRG 41635 Grupo de Investigación emergente.
  • Duración: 2009-2014

MAGING G PROTEINS IN CELL ADHESION AND MIGRATION

  • Financiado por: HELSE VEST 12458  NORWAY                
  • Duración: 2008-2010
  • Investigador Principal: A. M. Aragay 

 

 



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