Three-dimensional reconstruction of an unstimulated lymphocyte by X-ray cryotomography. Blue, reconstructed volume of the nucleus cell; red, mitochondria; green, position of the two centrioles of the centrosome that are surrounded by many proteins and, among them, the chaperonin CCT. Right: reconstructions of a lymphocyte forming an immune synapse where the polarization of the centrosome and mitochondria can be observed, concentrated on the synapse area.
Cerdanyola del Vallès, 9 December 2020 The T lymphocytes activation requires the interaction with antigen-presenting cells. The surface contact between both cells produces a structure called immune synapse, whose formation and dynamism determine the intensity of lymphocyte activation and the subsequent immune response.
This essential process for the immune response is very dynamic, since it requires the reorganization of the cytoskeleton and the centrosome, the region that controls the microtubules arrangement in the different phases of the cell cycle. Because of its importance, it is highly regulatedo.
Now, scientists from the Centro Nacional de Investigaciones Cardiovasculares (CNIC), the Instituto de Investigación Sanitaria del Hospital Universitario de La Princesa (IIS Princesa) and the National Centre for Biotechnology (CNB-CSIC), have identified the essential role of the cytosolic chaperonin CCT. The work, published in the journal Science Advances, reports how CCT controls the changes involved in the centrosome and mitochondria distribution through the production of cytoskeletal elements such as α - and β-tubulin
"CCT is involved in the folding of proteins that are very important for different cellular processes, mainly actin and tubulin, two essential proteins in the cytoskeleton formation", explains Javier Chichón, researcher at the CNB-CSIC. This new study proves its importance in processes where cell dynamism is critical.
X-rays cryotomography performed at the MISTRAL beamline of ALBA has enabled to observe the movements of the two centrioles of the centrosome and the changes in the mitochondria and microtubules distribution. This synchrotron light technique provides the possibility to completely observe cells, without needing to cut them, very close natural conditions. Apart from ALBA, this technology is only available in three other synchrotrons around the world (United Kingdom, Germany and the United States).
"Now, we know that CCT is responsible for all these changes. It controls the process by regulating the synthesis of α- and β-tubulin and the post-translational modifications necessary for microtubule assembly during immune synapse formation", explains Noa Martín, researcher at the IIS Princesa and the CNIC.
The new insights open the door to the design of strategies aimed at blocking CCT as a therapy against autoimmune processes that occur with hyperactivation of lymphoid cells.
Comparison of the centrosome (green) and mitochondria distribution (red) around the nucleus (blue) in activated and non-activated lymphocytes (right and left respectively).
Reference: N.B. Martín-Cofreces, F.J. Chichon, E. Calvo, D. Torralba, E. Bustos-Moran, S.G. Dosil, A. Rojas-Gómez, E. Bonzon-Kulichenko, J.A. López, J. Otón, A. Sorrentino, J.C. Zabala, I. Vernos, J. Vazquez, J.M. Valpuesta, F. Sánchez-Madrid. The chaperonin CCT controls T cell receptor-driven 3D configuration of centrioles. Science Advances (6), 49. DOI: 10.1126/sciadv.abb7242
This study has been possible also with the collaboration of the Universidad de Cantabria and the Centre de Regulació Genòmica of Barcelona.
