A new study describes a key molecular mechanism that explains how cells exchange information through extracellular vesicles (EVs), small particles with great therapeutic potential. The results, published in the Journal of Extracellular Vesicles , reveal that the Commander protein complex, previously known for its role in membrane recycling, also coordinates the entry and internal destination of vesicles within the cell. This finding sheds light on the process of intercellular communication, which is fundamental to the development of new therapies and diagnostic tools.
The study was led by Professor Albert Lu, from the Faculty of Medicine and Health Sciences of the UB and the CELLEX Biomedical Research Centre (IDIBAPS-UB), and María Yáñez-Mó, from the Severo Ochoa Centre for Molecular Biology (CSIC-UAM). Carles Enrich, professor at the same faculty (IDIBAPS-UB), also participated.
According to Albert Lu, "understanding how receptor cells capture and process extracellular vesicles is essential to understanding how our body communicates at the molecular level." "Furthermore - he continues - this knowledge is key to harnessing the therapeutic and diagnostic potential of these vesicles, since their effectiveness depends on being able to direct them and have them captured by the appropriate target cells."
An innovative methodology based on the CRISPR technique
Extracellular vesicles (EVs) are nanoparticles secreted by all cells that act as biological messengers: they transport proteins, lipids and nucleic acids. To identify the molecular mechanisms that direct their uptake and internalization in the cell, researchers have used an innovative methodological approach consisting of applying massive genomic screening based on CRISPR-Cas9 technology.
This tool allows researchers to deactivate each of the more than 20,000 human genes one by one, to analyse their role in the process. In this case, the researchers genetically modified the cells so that each group had a different gene deactivated. The cells were then exposed to EVs labelled with a fluorescent dye and, using flow cytometry, the cells that captured more or fewer vesicles were measured. Fluorescence-activated cell sorting (FACS) was then used to separate the cells with higher or lower uptake capacity. The deactivated genes in each group were subsequently identified using mass sequencing.
