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A. M. Aragay: Signaling through G proteins

Lab Presentation

The aim of this subline involves understanding the processes of signal transduction and the integration of signal transduction pathways that lead to changes in cell structure and function. Heterotrimeric G proteins are molecular switches that control a diverse array of biological processes. The cellular responses affected by the G protein coupled receptors are as diverse as visual perception, cell growth, neuromodulation, metabolism or immune response, among others. We focus our attention on the understanding of the signaling pathways that lead to changes in cell structure and in particular cell migration through changes in the actin filament organization in response to various stimuli.

Research Lines

The general objectives of the research subline are:

Effect of GPCR signaling in actin structure.
The ultimate goal is is to discern the link between receptor activation and actin fiber remodeling and cell motility, and, eventually, to understand the cellular responses to tissue damage and inflammation. The aims to be achieved are: to study the regulation of the chemokine response, in particular the regulation by endocytosis of activated receptors; to identify/characterize new signaling proteins in the chemokine pathway linked to actin fiber remodeling.
G proteins and cell migration.
One of the big opened questions in the G protein field was how a signal through the activation of a receptor (GPCR) can disrupt cell adhesion, reorganize actin fiber structure and induce migration. We hypothesized that the G12 family proteins were good candidates for these role. Our research brought to demonstrate that the G12 proteins bind to a protein involved in cell adhesion, the catenin p120. Our goals are to study the role of G12 and the catenin p120 in the regulation adherent junction disassembly.
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

  • Georgina Garrido

    PhD Student

  • Míriam Masià

    PhD Student

  • Cristiane Beninca

    PhD Student

  • 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.

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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