Browsing by Author "Vale-Costa, Silvia"
Now showing 1 - 2 of 2
Results Per Page
Sort Options
- Defining basic rules for hardening influenza A virus liquid condensatesPublication . Etibor, Temitope Akhigbe; Vale-Costa, Silvia; Sridharan, Sindhuja; Brás, Daniela; Becher, Isabelle; Mello, Victor Hugo; Ferreira, Filipe; Alenquer, Marta; Savitski, Mikhail M; Amorim, Maria-JoãoIn biological systems, liquid and solid-like biomolecular condensates may contain the same molecules but their behaviour, including movement, elasticity and viscosity, is different on account of distinct physicochemical properties. As such, it is known that phase transitions affect the function of biological condensates and that material properties can be tuned by several factors including temperature, concentration and valency. It is, however, unclear if some factors are more efficient than others at regulating their behaviour. Viral infections are good systems to address this question as they form condensates de novo as part of their replication programmes. Here, we used influenza A virus liquid cytosolic condensates, A.K.A viral inclusions, to provide a proof of concept that liquid condensate hardening via changes in the valency of its components is more efficient than altering their concentration or the temperature of the cell. Liquid IAV inclusions may be hardened by targeting vRNP interactions via the known NP oligomerizing molecule, nucleozin, both in vitro and in vivo without affecting host proteome abundance nor solubility. This study is a starting point for understanding how to pharmacologically modulate the material properties of IAV inclusions and may offer opportunities for alternative antiviral strategies.
- PI4P and BLOC-1 remodel endosomal membranes into tubulesPublication . Jani, Riddhi Atul; Di Cicco, Aurélie; Keren-Kaplan, Tal; Vale-Costa, Silvia; Hamaoui, Daniel; Hurbain, Ilse; Tsai, Feng-Ching; Dimarco, Mathilde; Macé, Anne-Sophie; Zhu, Yueyao; Amorim, Maria João; Bassereau, Patricia; Bonifacino, Juan; Subtil, Agathe; Marks, Michael; Lévy, Daniel; Raposo, Graça; Delevoye, CédricIntracellular trafficking is mediated by transport carriers that originate by membrane remodeling from donor organelles. Tubular carriers contribute to the flux of membrane lipids and proteins to acceptor organelles, but how lipids and proteins impose a tubular geometry on the carriers is incompletely understood. Using imaging approaches on cells and in vitro membrane systems, we show that phosphatidylinositol-4-phosphate (PI4P) and biogenesis of lysosome-related organelles complex 1 (BLOC-1) govern the formation, stability, and functions of recycling endosomal tubules. In vitro, BLOC-1 binds and tubulates negatively charged membranes, including those containing PI4P. In cells, endosomal PI4P production by type II PI4-kinases is needed to form and stabilize BLOC-1-dependent recycling endosomal tubules. Decreased PI4KIIs expression impairs the recycling of endosomal cargoes and the life cycles of intracellular pathogens such as Chlamydia bacteria and influenza virus that exploit the membrane dynamics of recycling endosomes. This study demonstrates how a phospholipid and a protein complex coordinate the remodeling of cellular membranes into functional tubules.