@article{TzonevaStoyanovaPetrichetal.2020,
  author    = {Tzoneva, Rumiana and Stoyanova, Tihomira and Petrich, Annett and Popova, Desislava and Uzunova, Veselina and Momchilova, Albena and Chiantia, Salvatore},
  title     = {Effect of Erufosine on Membrane Lipid Order in Breast Cancer Cell Models},
  series = {Biomolecules},
  volume    = {10},
  journal   = {Biomolecules},
  number    = {5},
  publisher = {MDPI},
  address   = {Basel},
  issn      = {2218-273X},
  doi       = {10.3390/biom10050802},
  pages     = {17},
  year      = {2020},
  abstract  = {Alkylphospholipids are a novel class of antineoplastic drugs showing remarkable therapeutic potential. Among them, erufosine (EPC3) is a promising drug for the treatment of several types of tumors. While EPC3 is supposed to exert its function by interacting with lipid membranes, the exact molecular mechanisms involved are not known yet. In this work, we applied a combination of several fluorescence microscopy and analytical chemistry approaches (i.e., scanning fluorescence correlation spectroscopy, line-scan fluorescence correlation spectroscopy, generalized polarization imaging, as well as thin layer and gas chromatography) to quantify the effect of EPC3 in biophysical models of the plasma membrane, as well as in cancer cell lines. Our results indicate that EPC3 affects lipid-lipid interactions in cellular membranes by decreasing lipid packing and increasing membrane disorder and fluidity. As a consequence of these alterations in the lateral organization of lipid bilayers, the diffusive dynamics of membrane proteins are also significantly increased. Taken together, these findings suggest that the mechanism of action of EPC3 could be linked to its effects on fundamental biophysical properties of lipid membranes, as well as on lipid metabolism in cancer cells.},
  language  = {en}
}
@article{PetazziKoikkarahAjiTischleretal.2021,
  author    = {Petazzi, Roberto Arturo and Koikkarah Aji, Amit and Tischler, Nicole D. and Chiantia, Salvatore},
  title     = {Detection of envelope glycoprotein assembly from old world hantaviruses in the Golgi apparatus of living cells},
  series = {Journal of virology},
  volume    = {95},
  journal   = {Journal of virology},
  number    = {4},
  publisher = {American Society for Microbiology},
  address   = {Baltimore, Md.},
  issn      = {1098-5514},
  doi       = {10.1128/JVI.01238-20},
  pages     = {18},
  year      = {2021},
  abstract  = {Hantaviruses are emerging pathogens that occasionally cause deadly outbreaks in the human population. While the structure of the viral envelope has been characterized with high precision, protein-protein interactions leading to the formation of new virions in infected cells are not fully understood. We used quantitative fluorescence microscopy (i.e., number and brightness analysis and fluorescence fluctuation spectroscopy) to monitor the interactions that lead to oligomeric spike complex formation in the physiological context of living cells. To this aim, we quantified protein-protein interactions for the glycoproteins Gn and Gc from Puumala and Hantaan orthohantaviruses in several cellular models. The oligomerization of each protein was analyzed in relation to subcellular localization, concentration, and the concentration of its interaction partner. Our results indicate that, when expressed separately, Gn and Gc form, respectively, homo-tetrameric and homo-dimeric complexes, in a concentration-dependent manner. Site-directed mutations or deletion mutants showed the specificity of their homotypic interactions. When both glycoproteins were coexpressed, we observed in the Golgi apparatus clear indication of GnGc interactions and the formation of Gn-Gc multimeric protein complexes of different sizes, while using various labeling schemes to minimize the influence of the fluorescent tags. Such large glycoprotein multimers may be identified as multiple Gn viral spikes interconnected via Gc-Gc contacts. This observation provides the possible first evidence for the initial assembly steps of the viral envelope within this organelle, and does so directly in living cells. <br /> IMPORTANCE In this work, we investigate protein-protein interactions that drive the assembly of the hantavirus envelope. These emerging pathogens have the potential to cause deadly outbreaks in the human population. Therefore, it is important to improve our quantitative understanding of the viral assembly process in infected cells, from a molecular point of view. By applying advanced fluorescence microscopy methods, we monitored the formation of viral spike complexes in different cell types. Our data support a model for hantavirus assembly according to which viral spikes are formed via the clustering of hetero-dimers of the two viral glycoproteins Gn and Gc. Furthermore, the observation of large Gn-Gc hetero-multimers provide the possible first evidence for the initial assembly steps of the viral envelope, directly in the Golgi apparatus of living cells.},
  language  = {en}
}