Intercellular communication in inflammatory response

Over the last few years, the group's research has addressed two main aspects:

  1. Intracellular connections of tetraspanins, in close collaboration with J. Vázquez's group.
  2. Functional association of tetraspanins with proteases. Several collaborations have also been maintained with IVI (Valencia), with the aim of extrapolating the role of tetraspanin adhesion platforms in the embryo implantation process.

The group's data on the characterisation of the intracellular interactome of microdomains enriched in tetraspanins revealed the role of these specialised adhesion platforms in exosome recruitment of adhesion receptors and, unexpectedly, RNA-binding proteins. Thus, 45% of the proteome in these extracellular vesicles (EVs) was connected to tetraspanin-enriched microdomains and the deletion of a single tetraspanin was sufficient to selectively reduce the incorporation of exosome-associated molecules.

Our future work aims to use all the tools available in the laboratory against tetraspanin molecules and their associated partners (metalloproteinases and adhesion receptors) to study their functional role in the biogenesis and function of EVs. This information will be critical to optimise therapies based on EVs, since it will reveal new therapeutic targets to block their secretion, diminish their metastatic or angiogenic capacities, or increase their stability and immunoregulatory potential.

Team members

area1-Linea-1_G3_Dra-Yañez-MoGroup leader:

María Yáñez Mó

Hospital Universitario Santa Cristina.

  Other team members:

  • Soraya López Martín.Hospital Universitario Santa Cristina.
  • Carla Mazzeo. Universidad Autónoma de Madrid.
  • Henar Suárez Montero.Hospital Universitario La Princesa.

Yañez Mó, María. Immunoregulatory molecules as biomarkers predicting response to biological therapies and disease severity in immune-mediated inflammatory disorders. BIOMID PROJECT. PIE13/00041. Coordinated project. ISCIII. 2014-2016.

Yañez Mó, María. Optimización de exomas para su uso en terapias. Papel de los microdominios ricos en tetraspaninos en la biogénesis y función de los exomas. Fundación Ramón Areces. 2015-2017.

Yañez Mó, María. Papel de los microdominios ricos en tetraspaninas y proteasas asociadas en la biogénesis y función de los exosomas. BFU2014-55478-R. MINECO. 2015-2017.

Yañez Mó, María. Analysis of the anti-metastatic activity of cytopermeable peptides that inhibit exosome secretion. Fundación BBVA. 2015-2016.

Yañez Mó, María. Estudio del potencial biotecnológico de herramientas frente a tetraspaninas en cáncer, secreción de exosomas y agentes vacunales. BIO2017-86500-R. Spanish State Research Agency. 2018-2020.

Andreu Z, Yáñez-Mó M. Tetraspanins in extracellular vesicle formation and function. Front Immunol 2015. 5: 442-0. PMID: 24723389. DOI: 10.1002/eji.201344235.

Perez-Hernandez D, Gutiérrez-Vázquez C, Jorge I, López-Martín S, Ursa A, Sánchez-Madrid F, Vázquez J, Yáñez-Mó M. The Intracellular Interactome of Tetraspanin-enriched Microdomains Reveals Their Function as Sorting Machineries toward Exosomes. J. Biol. Chem. 2013. 288: 11649-11661. FI: 4.600(Q1). PMID: 23463506. DOI: 10.1074/jbc.M112.445304.

Tejera E, Rocha-Perugini V, López-Martín S, Pérez-Hernández D, Bachir AI, Horwitz AR, Vázquez J, Sánchez-Madrid F, Yáñez-Mo M. CD81 regulates cell migration through its association with Rac GTPase. Mol. Biol. Cell 2013. 24: 261-273. FI: 4.548(Q2). PMID: 23264468. DOI: 10.1091/mbc.E12-09-0642.

Sala-Valdés M, Gordón-Alonso M, Tejera E, Ibáñez A, Cabrero JR, Ursa A, Mittelbrunn M, Lozano F, Sánchez-Madrid F, Yáñez-Mó M. Association of syntenin-1 with M-RIP polarizes Rac-1 activation during chemotaxis and immune interactions. J Cell Sci 2012. 125: 1235-1246. FI: 5.877(Q1). PMID: 22349701. DOI: 10.1242/jcs.094912.

Gordón-Alonso M, Sala-Valdés M, Rocha-Perugini V, Pérez-Hernández D, López-Martín S, Ursa A, Alvarez S, Kolesnikova TV, Vázquez J, Sánchez-Madrid F, Yáñez-Mó M. EWI-2 Association with alpha-Actinin Regulates T Cell Immune Synapses and HIV Viral Infection. J Immunol 2012. 189: 689-700. FI: 5.520(Q1). PMID: 22689882. DOI: 10.4049/jimmunol.1103708.