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Astrocytes and neurons: extracellular vesicles move like this

13 July 2021
The new research has been published in the "Journal of Extracellular Vesicles"

They are widely known as "extracellular vesicles" (EVs), and cells release them to communicate with each other. This also happens in our central nervous system, in both normal and pathological conditions, when these spherical carriers move along nerve cells to reach specific sites and deliver their messages. Until now, the mechanism by which this motion takes place has remained a mystery.

New research published in the "Journal of Extracellular Vesicles" has shed light on this subject by focusing on larger EVs, which have tended to receive less attention. The research investigated communication between specific cells, called astrocytes, and neurons. Using sophisticated optical instruments, SISSA scientists from prof. Giuseppe Legname’s group and the CNR Institute of Neuroscience (Dr Claudia Verderio’s group) were able to discover that movement along the cell surface occurs by means of specific molecular processes.

In particular, the scientists discovered that passive flow along neurons occurs through the binding of the prion protein molecule PrP present on the vesicle - the same molecule that is responsible in mutated form for prion diseases - with a receptor found on the surface of the nerve cell. Movement is thought to be possible in opposite directions. The scientists believe that this strategy operates alongside that employed by a smaller fraction of EVs that are able to move independently, thanks to the presence of actin filaments.

The authors of the research explain that these “results unveil, for the first time, a dual mechanism exploited by astrocytic large EVs to passively/actively reach target sites on neurons moving on the neuron surface. Our work has also revealed the role of PrP molecules in this process”. This discovery may also have important therapeutic repercussions. In fact, it has been shown that EVs are carriers of various pathogenic molecules, including those characteristic of diseases such as Alzheimer's: "PrP and its neuronal interactors could become potential targets to limit diffusion of toxic amyloid proteins in patients affected by neurodegenerative diseases, providing us with a completely new weapon. More generally," the researchers conclude, “extracellular motion, the characteristics of which we have outlined with this work, may be a common feature of various types of cells, including cancer and immune cells, and may therefore have a general role in the propagation of pathogenic signals. This is certain to be the subject of future research".

Full paper