Nogo-A is secreted in extracellular vesicles, occurs in blood and can influence vascular permeability

Rust, Ruslan and Holm, Mea M. and Egger, Matteo and Weinmann, Oliver and van, Rossum Danielle and Walter, Fruzsina and Santa Maria, Anaraquel and Gronnert, Lisa and Maurer, Michael A. and Kraler, Simon and Akhmedov, Alexander and Cideciyan, Rose and Luscher, Thomas F. and Deli, Mária Anna and Herrmann, Inge K. and Schwab, Martin E. (2024) Nogo-A is secreted in extracellular vesicles, occurs in blood and can influence vascular permeability. JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 44 (6). pp. 938-954. ISSN 0271-678X

Preview

Text RustR_Nogo-A.pdf - Published Version Available under License Creative Commons Attribution Non-commercial. Download (2MB) | Preview

Abstract

Nogo-A is a transmembrane protein with multiple functions in the central nervous system (CNS), including restriction of neurite growth and synaptic plasticity. Thus far, Nogo-A has been predominantly considered a cell contact-dependent ligand signaling via cell surface receptors. Here, we show that Nogo-A can be secreted by cultured cells of neuronal and glial origin in association with extracellular vesicles (EVs). Neuron- and oligodendrocyte-derived Nogo-A containing EVs inhibited fibroblast spreading, and this effect was partially reversed by Nogo-A receptor S1PR2 blockage. EVs purified from HEK cells only inhibited fibroblast spreading upon Nogo-A over-expression. Nogo-A-containing EVs were found in vivo in the blood of healthy mice and rats, as well as in human plasma. Blood Nogo-A concentrations were elevated after acute stroke lesions in mice and rats. Nogo-A active peptides decreased barrier integrity in an in vitro blood-brain barrier model. Stroked mice showed increased dye permeability in peripheral organs when tested 2 weeks after injury. In the Miles assay, an in vivo test to assess leakage of the skin vasculature, a Nogo-A active peptide increased dye permeability. These findings suggest that blood borne, possibly EV-associated Nogo-A could exert long-range regulatory actions on vascular permeability.

Actions (login required)

Edit Item