Joint MRC Protein Phosphorylation and Ubiquitylation, Cell Signalling and Immunology and Tayside Immunology Group Seminar
T and B lymphocytes are key players of the adaptive immune system. They recognize pathogenic cues via the T cell receptor (TCR) and the B cell receptor (BCR) to get activated and execute their protective function. TCR and BCR signaling are initiated at the plasma membrane and subsequently propagated into the cell, ultimately leading to cell activation and a protective immune response. However, inappropriate activation of T and B cells can be detrimental to the host resulting in autoimmune disorders, immunodeficiencies and cancer.
The TCR and BCR are located at the plasma membrane, which composition is highly heterogenic. Membrane compartmentalization based on specific lipid-lipid and protein-lipid interactions has raised the interest of the scientific community, converting the plasma membrane into an active player in the initiation of signaling, and adding an additional layer of regulation to our current understanding of the functioning of antigen receptors. Caveolin-1 is an integral membrane protein and a crucial component of caveolae. It has been long thought that lymphocytes lack Caveolin-1 expression, due to the absence of detectable caveolae in lymphocytes and the failure to detect Caveolin-1 in T and B cell lines. However, Caveolin-1 is expressed at low levels in primary lymphocytes, and recent studies have shown the importance of Caveolin-1 for the basal membrane organization of the BCR and the TCR as well as their reorganization upon activation.
Here, I will present two stories that highlight the importance of Caveolin-1 expression in lymphocytes in homeostasis and diseases. In particular, Caveolin-1 plays a previously unnoticed role fine-tuning the initial signaling events of TCR and BCR activation and thereby, controls cell-fate decision in T and B lymphocytes.
Dr. Minguet did her PhD (2002) in the Centro de Biología Molecular Severo Ochoa (Madrid, Spain) working on the identification of haematopoietic progenitors in embryonic tissues. As a postdoc in the Max-Planck Institute in Freiburg, she investigated the structure of immunoreceptors, the requirements for their activation and the signalling pathways downstream of those receptors. In 2008 She was awarded a Ramon y Cajal fellowship to work as an independent postdoc in Centro Nacional de Investigaciones Cardiovasculares (CNIC, Spain), where she started her work on Caveolins as intrinsic regulators of the immune system and in tumour biology. Since 2012, she has had her own group at the University of Freiburg, Germany, where she continues to explore the role of Caveolins and the molecular mechanisms leading to the activation of B and T lymphocytes.