Objective Cell-cell synapses are an exquisitely evolved means of communication between cells. During the formation of the immune synapse (IS), diverse transmembrane and membrane associated molecules are reorganized into a highly segregated structure at the T cell–Antigen-Presenting Cell (APC) contact site. As part of this process, the tubulin cytoskeleton is vectorially directed toward the center of the IS, where the microtubule-organizing center (MTOC) localizes. MTOC translocation is an early event in IS formation that brings the secretory apparatus into close apposition with the APC, thus providing the basis for polarized secretion.The proposal aims to define how the MTOC controls cytoskeletal rearrangement and communication at the IS, as a mechanism for macromolecule transport and nucleation of signalling molecules during synaptic contact. We will study the mechanisms of MTOC-mediated polarization of multivesicular bodies (MVB) and exosome delivery during IS formation, and will assess the role in these processes of MTOC translocation regulators (HDAC6) and microtubule (MT) polymerization promoters (Plk1 and EB1). MTOC-dependent mitochondrial polarization to the IS will be assessed as a bioenergetic source for cytoskeletal rearrangements, IS maturation and polarized exosomal delivery. In particular, our proposed study of the possible horizontal transfer of miRNAs during cognate interactions between immune cells has the potential to reveal how miRNAs can control the early initiation of immunity. We will investigate the mechanism of directional transfer of RNA-harbouring exosomes at the IS from T cell to APC, and will examine the functional consequences of this transfer on APC biology and on the immune response. These studies will open avenues for the treatment of immune-related diseases. Fields of science natural sciencesbiological sciencescell biologymedical and health sciencesbasic medicineimmunology Programme(s) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Topic(s) ERC-AG-LS6 - ERC Advanced Grant - Immunity and infection Call for proposal ERC-2011-ADG_20110310 See other projects for this call Funding Scheme ERC-AG - ERC Advanced Grant Coordinator CENTRO NACIONAL DE INVESTIGACIONES CARDIOVASCULARES CARLOS III (F.S.P.) Address Calle melchor fernandez almagro 3 28029 Madrid Spain See on map Region Comunidad de Madrid Comunidad de Madrid Madrid Activity type Research Organisations Principal investigator Francisco Sánchez Madrid (Prof.) Administrative Contact Inga Dreville (Ms.) Links Contact the organisation Opens in new window Website Opens in new window EU contribution No data Beneficiaries (2) Sort alphabetically Sort by EU Contribution Expand all Collapse all CENTRO NACIONAL DE INVESTIGACIONES CARDIOVASCULARES CARLOS III (F.S.P.) Spain EU contribution € 1 512 000,00 Address Calle melchor fernandez almagro 3 28029 Madrid See on map Region Comunidad de Madrid Comunidad de Madrid Madrid Activity type Research Organisations Principal investigator Francisco Sánchez Madrid (Prof.) Administrative Contact Inga Dreville (Ms.) Links Contact the organisation Opens in new window Website Opens in new window Other funding No data UNIVERSIDAD AUTONOMA DE MADRID Spain EU contribution € 499 200,00 Address Calle einstein 3 ciudad univ cantoblanco rectorado 28049 Madrid See on map Region Comunidad de Madrid Comunidad de Madrid Madrid Activity type Higher or Secondary Education Establishments Administrative Contact Mª Carmen Puerta (Ms.) Links Contact the organisation Opens in new window Website Opens in new window Other funding No data
