Selected Publications
- Bertolotti M, Farinelli G, Galli M, Aiuti A, Sitia R., AQP8 transports NOX2-generated H2O2 across the plasma membrane to promote signaling in B cells. J Leukoc Biol. 2016
- Bertolotti M., Bestetti S, García-Manteiga JM, Medraño-Fernandez I, Dal Mas A, Malosio ML, Sitia R., Tyrosine kinase signal modulation: a matter of H2O2 membrane permeability? Antioxid Redox Signal. 2013 Nov;19(13):1447-51.
- Bertolotti M., Sitia R, Rubartelli A, On the redox control of B lymphocyte differentiation and function Antioxid Redox Signal. 2012 May;16(10):1139-49.
- Bertolotti M., Yim Sh, Garcia-Manteiga Jm, Masciarelli S, Kim Yj, Kang Mh, Iuchi Y, Fujii J, Vené R, Rubartelli A, Rhee Sg, Sitia R, B to plasma cell terminal differentiation entails oxidative stress and profound reshaping of the antioxidant responses, Antioxid Redox Signal. 2010 Oct;13(8):1133-44.
- Masciarelli S, Fra AM, Pengo N, Bertolotti M, Cenci S, Fagioli C, Ron D, Hendershot LM and Sitia R, CHOP-independent apoptosis and pathway-selective induction of the UPR in developing plasma cells, Mol Immunol. 2010 Mar;47(6):1356-65
FRIAS Project
Mapping the nanoscale organization of the BCR redox machinery
Through the B cell antigen receptor (BCR) mature B cells recognize the presence of antigens in the external world and adapt their responses. The signaling output from this receptor is tightly controlled by co-stimulatory and inhibitory receptors, so as to prevent its hypo- or hyper-stimulation, respectively. The host lab has employed a Fab-based proximity ligation assay (Fab-PLA) that allows a precise mapping of the localization and interactions of proteins on the B cell surface at nm distances. It is known that reactive oxygen species (ROS) can amplify BCR signaling. However, ROS fluxes have never been studied at the nanoscale level. I recently showed that the NADPH oxidase complex 2 (NOX2) produces ROS molecules, such as H2O2, on the B cell surface and that the water channel aquaporin 8 (AQP8) is consequently needed to transport H2O2 through the plasma membrane for BCR signal amplification. A major open question in the redox field is the nanoscale organization of the signaling components. Furthermore, little is known about the nanoscale location and interactions of BCR inhibitory receptors, and the second aim of my research project is to thoroughly investigate this issue. My project will provide new insights on normal B cells membrane organization and signaling mechanisms, and consequently on the molecular background associated with diseases such as B cell leukemia.