title: Microtubule-associated protein-4 controls nanovesicle dynamics and T cell activation.
abstract: The immune synapse (IS) is a specialized structure formed at the contact area between T lymphocytes and antigen-presenting cells (APCs) that is essential for the adaptive immune response. Proper T cell activation requires its polarization towards the APC, which is highly dependent on the tubulin cytoskeleton. Microtubule-associated protein-4 (MAP4) is a microtubule (MT)-stabilizing protein that controls MTs in physiological processes, such as cell division, migration, vesicular transport or primary cilia formation. In this study, we assessed the role of MAP4 in T cell activation. MAP4 decorates the pericentrosomal area and MTs of the T cell, and it is involved in MT detyrosination and stable assembly in response to T cell activation. In addition, MAP4 prompts the timely translocation of the MT-organizing center (MTOC) towards the IS and the dynamics of signaling nanovesicles that sustains T cell activation. However, MAP4 acts as a negative regulator of other T cell activation-related signals, including diacylglycerol (DAG) production and IL2 secretion. Our data indicate that MAP4 acts as a checkpoint molecule that balances positive and negative hallmarks of T cell activation.
authors.affiliation: Laboratory of Intercellular communication, Fundación CNIC, Madrid 28029, Spain.|Servicio de Inmunología, Hospital Universitario de la Princesa, UAM, IIS-IP, Madrid 28006, Spain.
authors.forename: Eugenio
authors.initials: E
authors.lastname: Bustos-Morán
authors.affiliation: Laboratory of Intercellular communication, Fundación CNIC, Madrid 28029, Spain.|Servicio de Inmunología, Hospital Universitario de la Princesa, UAM, IIS-IP, Madrid 28006, Spain.
authors.forename: Noelia
authors.initials: N
authors.lastname: Blas-Rus
authors.affiliation: Laboratory of Intercellular communication, Fundación CNIC, Madrid 28029, Spain.|Servicio de Inmunología, Hospital Universitario de la Princesa, UAM, IIS-IP, Madrid 28006, Spain.|CIBER Cardiovascular, ISCIII, Madrid, 28029, Spain.
authors.forename: Noa Beatriz
authors.initials: NB
authors.lastname: Martin-Cófreces
authors.affiliation: Laboratory of Intercellular communication, Fundación CNIC, Madrid 28029, Spain fsmadrid@salud.madrid.org.|Servicio de Inmunología, Hospital Universitario de la Princesa, UAM, IIS-IP, Madrid 28006, Spain.|CIBER Cardiovascular, ISCIII, Madrid, 28029, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Sánchez-Madrid
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D004075:Diglycerides / Q000378:metabolism; D006801:Humans; D054992:Immunological Synapses / Q000378:metabolism; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000276:immunology*; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D022101:Microtubule-Organizing Center / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism*; D053758:Nanoparticles / Q000737:chemistry*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*; D022161:Transport Vesicles / Q000378:metabolism*
chemical_list: C011439:1,2-diacylglycerol; D015415:Biomarkers; D004075:Diglycerides; C000601103:MAP4 protein, human; D008869:Microtubule-Associated Proteins; D011948:Receptors, Antigen, T-Cell
keywords: MAP4; Microtubules; T cell activation; Vesicle dynamics