Immune Cell-to-Cell communication: Mechanisms of microRNA and proteins sorting into exosomes
Dates: | 17 May 2016 |
Times: | 13:00 - 14:00 |
What is it: | Seminar |
Organiser: | Faculty of Life Sciences |
Who is it for: | University staff, Current University students |
Speaker: | Professor Francisco Sanchez-Madrid |
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Exosomes are released by most cells to the extracellular environment and are involved in cell-to-cell communication, mediating transfer of proteins and RNAs through structures as the Immunological synapse. Exosomes arising from different cell types show enrichment for a shared set of specific proteins, including tetraspanins, adhesion molecules, endosomal proteins, and heat-shock proteins, among others. They are also very much enriched in RNAs, including miRNAs and other non-coding RNAs. Exosome composition is not a mere copy of cytosolic content; rather, specific proteins and nucleic acids are selectively sorted into exosomes. The amount and content of exosomes can moreover change in response to stimuli such as cell activation, hypoxia or cell stress. Such changes in exosome composition determine the final outcome of exosome-mediated communication. However, the mechanisms that control these processes are not well understood.
First, the mechanisms of miRNA sorting into EVs will be discussed. In this regard, we have identified sequence motifs present in miRNAs that control their localization into exosomes. The protein heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1) specifically binds exosomal miRNAs through the recognition of these motifs and controls their loading into exosomes. Moreover, hnRNPA2B1 in exosomes is sumoylated, and sumoylation controls the binding of hnRNPA2B1 to miRNAs. Second, post-translational modifications of proteins that control exosomal sorting will be described. Our recent data demonstrate that ISGylation, an ubiquitin-like modification, controls exosome secretion.
Speaker
Professor Francisco Sanchez-Madrid
Organisation: Universidad Autonoma de Madrid
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Michael Smith Lecture Theatre
Michael Smith Building
Manchester