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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.

Projects

Research Lines:

  • 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.

Lab people

Principal investigator

Anna M. Aragay is the head of the “Signaling Transduction group” at IBMB-CSIC. She obtained her PhD. at the Autonomous University of Barcelona (UAB) in 1989. In 1990 she moved to the California Institute of Technology (Caltech) at USA for a postdoct with Prof. M. Simon where she focus her interest in signal transduction processes.

During this period she had a close collaboration with Prof. H. Brown at UCSD where she implemented microinjecting techniques for signal inhibition and with Prof. H. Lester at Caltech using electrophysiology for GPCR studies. In 1996, she joint the group of Prof. F. Mayor at CBM, Madrid, as a junior scientist, studying chemokine signaling.

As Associated Professor at the University of Bergen (UiB), Norway, she established her research group in 1999 and became Professor in 2005. For four years she directed the Norwegian National platform for Molecular Imaging (MIC). In mid-2006, she became “Científico titular” at IBMB where she established-back her actual group.

Past students

Mireia Andreu

PhD Student

Georgina Garrido

PhD Student

Míriam Masià

PhD Student

Cristiane Beninca

PhD Student

Selected publications

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.

All publications

An overview on G protein-coupled receptor-induced signal transduction in Acute Myeloid Leukemia. Selheim F, Aasebø E, Ribas C, Aragay AM.. Curr Med Chem 2019 Apr 29. 26(28):5293-5316.


Phosphorylation of Filamin A regulates chemokine receptor CCR2 recycling. Pons M, Izquierdo I, Andreu-Carbó M, Garrido G, Planagumà J, Muriel O, Geli MI, Aragay AM. J Cell Sci. 2017 Jan 15;130(2):490-501.


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


A new non-canonical pathway of Gα(q) protein regulating mitochondrial dynamics and bioenergetics. 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. Cell Signal. 2014 26:1135-46.
Gαq signalling: the new and the old. Sánchez-Fenández G, Cabezudo S, García-Hoz C, Benincá C, Aragay AM, Mayor F Jr, Ribas. Cell Signal. 2014 26:833-48.


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


A-hinge region1-EGFP: a novel tool for tracking the cellular functions of Filamin A in real-time. Planagumà J, Minsaas L, Pons M, Myhren L, Garrido G, Aragay AM.. PLoS One. 2012;7(8):e40864.


Gα(12) binds to the N-terminal regulatory domain of p120(ctn), and downregulates p120(ctn) tyrosine phsophorylation induced by Src family kinases via a RhoA indepnedent mechanism. Ardawatia VV, Masià-Balagué M, Krakstad BF, Johansson BB, Kreitzburg KM, Spriet E, Lewis AE, Meigs TE, Aragay AM. Exp Cell Res. 2011 Feb 1;317(3):293-306.


Filamin a binds to CCR2B and regulates its internalization.  Minsaas L, Planagumà J, Madziva M, Krakstad BF, Masià-Balagué M, Katz AA, Aragay AM.   PLoS One 2010 5(8):e12212
GRK2 negatively regulates chemokine activation of ERK cascade at a level downstream from G protein subunits. Jiménez-Sainz, MC., Murga, C., Kavelaars, A. , Jurado, M., Fast-Kraastak, B., Heijnen, C.J. Mayor,  F., Aragay, A. M. Mol. Biol. Cell  2006 Jan;17(1):25-31.


Proteosome involvement in Galphaq and Galpha16 protein degradation. B.B. Johannson, Minsaas L.  & Aragay, A.M. FEBS J. 2005. 272, 5365-5377.


A role for Ga12/Ga13 in p120ctn regulation. Krastad, B., V. Ardavatia & Aragay, AM. Proc. Natl. Acad. Sci., 2004 101, 10314-10319.


Mechanisms of the CCR2 chemokine receptor activation of the MAPK cascade. M.C. Jimenez, Fast, B, Mayor, F., jr. &  A.M.Aragay  Mol. Pharmacol. 2003. 64, 773-782.


Functional regulation of Galpha16 by protein Kinase C. Aragay AM, Quick MW. J. Biol. Chem. 1999 19;274(8):4807-15.


G protein-coupled receptro kinase 2 (GRK2): mechanisms of regulation and physiologycal functions. Aragay AM, Ruiz-Gómez A, Penela P, Sarnago S, Elorza A, Jiménez-Sainz MC, Mayor F Jr. FEBS Lett. 1998 Jun 23;430(1-2):37-40.


The chemokine monocyte chemoatactic protein 1 triggers Janus kinase 2 activation and tyrosine phsophorylation of the CCR2B receptor. Mellado M, Rodríguez-Frade JM, Aragay A, del Real G, Martín AM, Vila-Coro AJ, Serrano A, Mayor F Jr, Martínez-A C. J Immunol. 1998 Jul 15;161(2):805-13.


Monocyte chemoattractant protein-1-induced CCR2B receptor desensitization mediated by the G protein-coupled receptor kinase 2. Aragay AM, Mellado M, Frade JM, Martin AM, Jimenez-Sainz MC, Martinez-A C, Mayor F Jr. Proc Natl Acad Sci U S A. 11998 Mar 17;95(6):2985-90.


Desensitization of inositol 1,4,5-triphsopate/Ca2+-induced Cl- currents by prolonged activation of G proteins in Xenopus oocytes. Quick MW, Lester HA, Davidson N, Simon MI, Aragay AM. J Biol Chem. 1996 Dec 13;271(50):32021-7.


A novel form of the Gbeta5 is specifically expressed in teh vertebrate retina. Watson AJ, Aragay AM, Slepak VZ, Simon MI. J Biol Chem. 1996 Nov 8;271(45):28154-60.


Coupling of the thrombin receptor to G12 may account for the selective effects of thrombin on gene expression and DNA systhesis in 1321N1 astrocytoma cells. Post GR, Collins LR, Kennedy ED, Moskowitz SA, Aragay AM, Goldstein D, Brown JH. Mol Biol Cell. 1996 Nov;7(11):1679-90.


Cell-specific signal transduction of parathyroid hormone (PTH)-related protein through stabley expressed recombinant PTH/PTHrP receptros in vacular smooth muscle cells. Maeda S, Wu S, Jüppner H, Green J, Aragay AM, Fagin JA, Clemens TL. Endocrinology. 1996 Aug;137(8):3154-62.


Increase expression of alphaq family G-proteins during oocyte maturation and early development of Xenopus laevis. Gallo CJ, Jones TL, Aragay AM, Jaffe LA. Dev Biol. 1996 Jul 10;177(1):300-8.


G12 requirement for thrombin-stimulated gene exoression and DNA synthesis in 1321N1 astrocytoma cells. Aragay AM, Collins LR, Post GR, Watson AJ, Feramisco JR, Brown JH, Simon MI. J Biol Chem. 1995 Aug 25;270(34):20073-7.


Differential coupling of G protein alpha subunits to seven-helix receptors expressed in Xenopus oocytes. Quick MW, Simon MI, Davidson N, Lester HA, Aragay AM. J Biol Chem. 1994 Dec 2;269(48):30164-72.


Design of degenerate oligonucleotide primrs for cloning of G-protein alpha subunits. Wilkie TM, Aragay AM, Watson AJ, Simon MI. Methods Enzymol. 1994;237:327-44.


Random mutagenesis of G protein alpha subunits G(o)alpha. Mutations alterin nucleotide binding. Slepak VZ, Quick MW, Aragay AM, Davidson N, Lester HA, Simon MI. J Biol Chem. 1993 Oct 15;268(29):21889-94.


The G alpha q and G alpha 11 proteins couple the thyrotropin-releasing hormone receptor to phospholipase C in GH3 rat pituitary cells. Aragay AM, Katz A, Simon MI. J Biol Chem. 1992 Dec 15;267(35):24983-8.

Project funding

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

Vacancies/Jobs

We offer a PhD student position granted by the Spanish Ministry of Science and Innovation.  Applications will be considered ASAP.

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